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Background: Febrile neutropenia (FN) is a recognised adverse event associated with chemotherapy. This study investigates the impact of atezolizumab, an immune checkpoint inhibitor, on the incidence of FN in patients with non-small cell lung cancer receiving concurrent chemotherapy in Japan., Methods: This post-marketing database study was conducted using data from patients with non-small cell lung cancer provided by Medical Data Vision Co., Ltd. covering April 2008 to present. The primary outcome measured was FN incidence, and its causal association with atezolizumab use was examined by comparing the atezolizumab plus bevacizumab plus carboplatin plus paclitaxel [ABCP])-containing regimen to the BCP control group. The data period was from 1 September, 2015, to 31 December, 2021, including approval date of this drug, 21 December, 2018., Results: The database identified 301 subjects for the ABCP regimen (exposure) group, 44 for the BCP regimen (cohort design control) group during the same period, and 207 for BCP regimen (historical cohort design control) group before the approval of atezolizumab. For historical cohort design, the incidence and adjusted incidence ratios of febrile neutropenia in the exposure group to the control group were 6.13 (95% CI 2.78-13.49) and 8.19 (95% CI 3.79-25.33), respectively. Sensitivity analysis showed FN occurred in 17% (52/301) of the exposure group, 4.5% (2/44) of the cohort design control group, and 3% (7/207) of the historical cohort design control group., Conclusions: The incidence of FN was higher in the exposure group. Considering the study results, special caution is needed for FN occurrence in patients receiving atezolizumab., Competing Interests: Declarations. Conflict of interest: All the authors are employees of Chugai Pharmaceutical Co., Ltd. and have no conflicts of interest to disclose., (© 2024. The Author(s).)

Background: Most patients with small-cell lung cancer (SCLC) present with extensive-stage (ES) disease and have a poor prognosis despite achieving high initial response rates to platinum-based doublet chemotherapy. This study evaluated whether adding hydroxychloroquine (HCQ) to chemotherapy could improve outcomes., Methods: This was a randomised multicentre phase II trial. Eligible patients had untreated ES-SCLC, a performance status 0-2 and measurable disease. Patients were randomly assigned (1:1 ratio) to HCQ (400 mg orally twice daily) plus carboplatin-gemcitabine or carboplatin-etoposide alone. Chemotherapy was administered for up to six cycles, with HCQ given concurrently and then as single agent for up to 30 months. Primary endpoint was PFS, aiming for a hazard ratio (HR) of 0.70., Results: 72 patients were randomised (36 HCQ+chemotherapy and 36 chemotherapy alone). Median HCQ treatment duration was 4.4 months. HCQ did not improve PFS (HR 1·12 95 %CI 0·69-1.84; p = 0·64), with a median of 5.7 months (HCQ+chemotherapy) versus 6.2 months (chemotherapy). The corresponding median OS were 8.9 and 10.2 months (HR 0.83, 95 %CI 0.48-1.45, p = 0.52). Fewer patients in the HCQ arm completed four cycles of chemotherapy due to adverse events (64 % vs. 81 %). Grade ≥ 3 adverse events were higher in the HCQ+chemotherapy arm (83.3 % vs. 27.8 %), primarily anaemia, neutropenia, and thrombocytopenia, partly due to the initially higher gemcitabine dose used CONCLUSIONS: Combining HCQ with platinum doublet chemotherapy did not improve PFS or OS outcomes for ES-SCLC, resulting in more patients stopping chemotherapy due to increased adverse events. When considered alongside other randomised studies of HCQ in cancer, the evidence collectively indicates a limited role for HCQ as a therapeutic option., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The efficacy and feasibility of pembrolizumab combined with chemotherapy in frontline management of advanced high-grade epithelial ovarian cancer (EOC) is unknown. Additionally, modification of the tumor microenvironment following neoadjuvant therapy is not well understood., Methods: In this single-arm phase 2 trial (this study was registered at ClinicalTrials.gov: NCT02520154), eligible patients received up to 4 cycles of neoadjuvant chemotherapy followed by interval cytoreduction, 3 cycles of adjuvant intravenous carboplatin/weekly paclitaxel/pembrolizumab, and finally maintenance pembrolizumab until progression or toxicity (maximum 20 cycles). The primary endpoint was progression-free survival (PFS). Secondary endpoints included feasibility, toxicity, and overall survival (OS). PD-L1 staining, multiplex immunofluorescence staining, RNA sequencing, reverse-phase protein array analyses were performed on pre- and post-chemotherapy samples., Findings: Thirty-one eligible patients were enrolled. Median PFS and OS was 14.88 (95% CI 12.39-23.00) and 57.43 months (95% CI 30.88-not reached), respectively. Among those with PD-L1 combined positive score (CPS) ≥10, the median PFS and OS were not reached compared to those with CPS <10 (10.50 and 30.90 months, respectively). Feasibility was met, with all patients completing their planned adjuvant cycles. Treatment discontinuation due to immune-related toxicity occurred in 6 patients (20%). Chemotherapy resulted in an infiltration of anti-tumor immune cells in the tumor microenvironment. Samples of patients with the best PFS demonstrated increased expression of NF-κB, TGF-β, and β-catenin signaling., Conclusions: Pembrolizumab with chemotherapy was feasible and resulted in PFS within the historical range for this EOC population. Patients with CPS ≥10 may benefit more from this regimen, and future studies should investigate this potential biomarker., Funding: This investigator-initiated trial was funded by Merck., Competing Interests: Declaration of interests S.N.W. reports grants from NIH, GOG Foundation, Cotinga Pharmaceuticals, Bayer, and ArQule during the conduct of the study. She also reports grants and personal fees from AstraZeneca, Clovis Oncology, GlaxoSmithKline/Tesaro, Roche/Genentech, and Novartis. She reports personal fees from Merck, Pfizer, Eisai, CIrculogene, Zentalis, and Agenus outside the submitted work. N.D.F. reports personal fees from Tesaro, Pfizer, Bristol Myers Squibb, and GlaxoSmithKline outside the submitted work. A.K.S. discloses the following competing interests: consulting (Merck, GSK, ImmunoGen, Iylon, Kiyatec, Astra Zeneca, Onxeo) and shareholder (BioPath). R.C. reports the following competing interests: consulting (Clovis Oncology, Genentech/Roche, AstraZeneca/MedImmune, Genmab, OncoMed, Immunogen, AbbVie, Agenus, Novocure, Merck, OncXerna Therapeutics, Alkermes, Gradalis, GlaxoSmithKline, Alkermes, Eisai, GOG Foundation, Karyopharm Therapeutics), employment (Vanium Group, US Oncology Network), leadership (Onsexo), stock and other ownership interests (McKesson/US Oncology Network), and research funding (AstraZeneca/MedImmune, Clovis Oncology, Merck, Roche/Genentech, Immunogen, Mirati Therapeutics, Amgen, Pfizer, Lilly, Regeneron, Alkermes, Karyopharm Therapeutics). A.A.J. reports personal fees from Gerson Lehrman Group, Guidepoint, Iovance advisory board, NuProbe, Simcere, PACT Pharma, Genentech-Roche, Eisai, Agenus, and Macrogenics. He also reports grants from AstraZeneca, Bristol Myers Squibb, Iovance, Aravive, Pfizer, Immatics US, Eli Lilly, and Merck, and stock/stock options from AvengeBio outside the submitted work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Platinum-based chemotherapy is a mainstay of treatment for many childhood cancers but is associated with acute nephrotoxicity and long-term ototoxicity. There is emerging evidence of long-term renal complications. This study aimed to assess the prevalence of chronic kidney disease (CKD) in children treated with platinum chemotherapy (cisplatin and carboplatin) and identify potential risk factors for the development of CKD., Methods: We conducted a retrospective review of children diagnosed with hepatoblastoma, osteosarcoma, neuroblastoma, or medulloblastoma who received platinum chemotherapy over a 16 year timeframe. Patients were excluded if they did not have at least 3 years follow up data, died within 3 years of platinum chemotherapy, or if they relapsed. Clinical data were collected at baseline (first dose), 1 year, and at most recent follow up., Results: Of 328 treated patients, 147 met the inclusion criteria and were followed for a mean of 8.1 years (range 3-15.7 years). The median age at first dose was 3.7 years (IQR 1.7-9.6 years). CKD ≥grade 2 was present in 53(36%) at last follow up and 15(10%) had tubular dysfunction. A history of acute kidney injury at any time during treatment was associated with CKD (OR 3.12 CI 1.07-9.12, p =0.04). On multivariable analysis older age at platinum therapy (OR 1.2, CI 1.1-1.4, p = 0.004) and a high aminoglycoside or vancomycin trough level (OR 4.3, CI 1.9-9.7, p < 0.001) were risk factors for CKD., Conclusion: The high rate of CKD in children treated with platinum chemotherapy warrants long-term follow-up and screening for progressive disease., (© 2024 Wiley Periodicals LLC.)

Visual loss following secondary retinitis pigmentosa (RP) is a rare complication of cytotoxic chemotherapy. Few cases of docetaxel- and/or platinum-induced retinal toxicity have been reported. Routine ocular examination of patients undergoing chemotherapy is required for early recognition and intervention of ocular toxicity. A 72- year-old female undergoing docetaxel and carboplatin combination chemotherapy for the past 3 months presented with complaints of defective vision in both eyes for 2 months. Fundus examination revealed a waxy pale disc in both eyes, arteriolar attenuation, and peripheral bony spicules, suggesting secondary retinitis pigmentosa. Optical Coherence Tomography (OCT) of the macula revealed macular dystrophy. The Humphrey Visual Field (HVF) showed field defects. Despite the reduction in chemotherapy dosage, no improvement was observed during the threeweek follow-up period.

Objectives: Part 1 of the RUBY trial (NCT03981796) demonstrated improved survival in patients with primary advanced or recurrent endometrial cancer (EC) treated with dostarlimab plus carboplatin-paclitaxel versus placebo plus carboplatin-paclitaxel. Here, we examine additional efficacy and safety data from patients with mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) EC in the RUBY trial., Methods: Patients were randomized 1:1 to dostarlimab 500 mg or placebo plus carboplatin-paclitaxel every 3 weeks for 6 cycles followed by dostarlimab or placebo every 6 weeks for up to 3 years. In the dMMR/MSI-H population of RUBY Part 1, analysis of progression-free survival by investigator assessment compared with blinded independent central review, sensitivity analyses of the source-verified population compared with the randomized population, and analysis of safety in this population were completed., Results: In total, 118 patients with dMMR/MSI-H were enrolled in the RUBY trial (53, dostarlimab arm; 65, placebo arm). At the first interim analysis, a 72% reduction in the risk of progression or death (P < 0.0001) was seen with dostarlimab plus carboplatin-paclitaxel by investigator assessment per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), which was consistent with blinded independent central review per RECIST v1.1. Likewise, sensitivity analyses of the source-verified dMMR/MSI-H population compared with the randomized dMMR/MSI-H population were consistent for progression-free survival and overall survival. Safety results seen in the dMMR/MSI-H population were similar to those previously reported for the overall population., Conclusions: All primary and secondary efficacy assessments demonstrate the consistent benefit of dostarlimab plus carboplatin-paclitaxel. The improvements seen in survival and the manageable safety profile support the favorable benefit-risk profile for dostarlimab plus carboplatin-paclitaxel in patients with dMMR/MSI-H primary advanced or recurrent EC., Competing Interests: Declaration of competing interest Matthew A. Powell reports grants/research support from GSK and honoraria/consultation fees from AstraZeneca, Clovis Oncology, Eisai, GSK, ImmunoGen, and Merck. David Cibula reports participation on an advisory board from Akesobio, AstraZeneca, GSK, MSD, Novocure, Roche, Seagen, and Sotio. David M. O'Malley reports grants from Ajinomoto, BMS, Cerulean Pharma, GOG Foundation, INC Research, InVentiv Health Clinical, Iovance Biotherapeutics, Ludwig Cancer Research, New Mexico Cancer Care Alliance, PRA International, Serono, Stemcentrx, Tracon Pharmaceuticals, and Yale University; has been a consultant/advisory board member for AbbVie, Ambry, Amgen, Array Biopharma, Clovis Oncology, EMD Serono, Ergomed, Janssen/Johnson & Johnson, Myriad Genetics, Novocure, Regeneron, Tarveda, and VentiRx; was a member of a steering committee for Genentech/Roche and Merck; and received personal fees from Agenus, Eisai, GSK and ImmunoGen. Ingrid Boere reports institutional research grant from GSK and institutional advisory board meeting fees from AstraZeneca and GSK. Mark S. Shahin reports institutional grants from AstraZeneca, GSK, and Merck; honoraria from AstraZeneca, GSK, Merck, and Seagen; expert testimony fees from Robinson & Havens PSC, Lexington, KY; advisory board fees from Seagen; and board member for Unite for Her. Antonella Savarese reports institutional funding and provision of study materials from GSK and MSD; institutional funding and provision of study material for other clinical trials from GSK and MSD; honoraria from GSK and MSD; support for attending meetings and/or travel from GSK, MSD, and PharmaMar; and advisory board honoraria from Eisai and MSD. Dana M. Chase reports consultant fees from AstraZeneca and GSK and honoraria from AstraZeneca, GSK, ImmunoGen, and Seagen/Genmab. Lucy Gilbert reports institutional grants from Alkermes, AstraZeneca, Clovis Oncology, Corcept Therapeutics, Esperas, GOG Foundation, GSK, ImmunoGen, IMV, K-Group Beta, Karyopharm Therapeutics, MSD, Mersana Therapeutics, Novocure GmbH, OncoQuest Pharmaceuticals, Roche, Shattuck Labs, Sutro BioPharma, and Tesaro; consulting fees from GSK and Merck; honoraria from CanariaBio, Eisai, Eisai-Merck, GOG Foundation, GSK, ImmunoGen, Kora Healthcare, and Merck; travel support from EndomEra, GOG Foundation, GSK, Merck, and Zentalis; and participation on a data safety monitoring board or advisory board from CanariaBio, Eisai, Eisai-Merck, GOG Foundation, GSK, ImmunoGen, Kora Healthcare, and Merck. Destin Black reports institutional grant fees from GSK; fees for being a member of GOG Partners Investigational Council; and medical director/owner of Trials365, LLC. Jørn Herrstedt reports consultant fees from Elsai. Sudarshan Sharma has nothing to disclose. Stefan Kommoss reports grants from GSK; consulting fees from AstraZeneca, Eisai, GSK, MSD, and Roche; and participating on a data safety monitoring board or advisory board for AstraZeneca, GSK, MSD, and Roche. Michael A. Gold has nothing to disclose. Anna M. Thijs has nothing to disclose. Kari Ring has nothing to disclose. Magnus Frödin Bolling reports press-release comment fees from GSK. Joseph Buscema reports honorarium for participation in an advisory committee from GSK. Sarah E. Gill has nothing to disclose. Paul Nowicki has nothing to disclose. Nicole Nevadunsky has nothing to disclose. Michael Callahan has nothing to disclose. Lyndsay Willmott reports speakers' bureau fees from AstraZeneca, Eisai, ImmunoGen, Merck, and Seagen and advisory board fees from AstraZeneca, ImmunoGen, and Seagen. Carolyn McCourt reports personal royalties <$200 annually from UpToDate and personal honoraria of $200 from the Washington University OB/Gyn annual symposium. Caroline Billingsley has nothing to disclose. Sharad A. Ghamande reports institutional fees from the Georgia Cancer Center for trial and consulting and speakers' bureau fees from GSK and Eisai. Zangdong He, Morad Marco Balas, and Shadi Stevens are employees of GSK. Evelyn Fleming has nothing to disclose. Mansoor Raza Mirza reports reports consulting fees from AstraZeneca, Biocad, GSK, Karyopharm Therapeutics, Merck, Roche, and Zailab; speakers' bureau fees from AstraZeneca and GSK; research funding (to institution) from Apexigen, AstraZeneca, Deciphera (trial chair), GSK, and Ultimovacs; and personal financial interest in Karyopharm Therapeutics (stocks/shares, member of board of directors)., (Copyright © 2024. Published by Elsevier Inc.)

Immune checkpoint inhibitors (ICIs), such as pembrolizumab (PEM), are widely recognized for their antitumor efficacy, but they can also lead to various cutaneous adverse events (CAEs). While most CAEs can be managed with topical corticosteroids, severe cases may necessitate halting immunotherapy. The incidence of severe CAEs is notably higher in combination therapies involving ICIs than in monotherapies, emphasizing the need for stringent, long-term management strategies. This includes potential modifications or discontinuations of the combination therapy. PEM, when added to the conventional paclitaxel + cisplatin (or carboplatin) ± bevacizumab regimen, has shown significant improvements in overall and progression-free survival for patients with Stage IVB metastatic or locally uncontrolled recurrent cervical cancer. This case series retrospectively examined the incidence and management of CAEs in 19 female patients treated with this combination therapy between October 2022 and May 2023. Four patients exhibiting CTCAE grade 3 were identified. The four cases of severe CAEs involved erythema multiforme after the initial course of PEM combination chemotherapy. Notably, three patients experienced immediate hypersensitivity reactions, including anaphylaxis, during subsequent treatments. This observation underscores the necessity for rigorous dermatological monitoring of patients undergoing PEM combination chemotherapy. Such vigilance is crucial for early detection of adverse reactions and timely adjustment of treatment regimens, thereby enhancing patient safety., (© 2024 The Author(s). The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.)

Purpose: To determine whether the administration of intra-arterial carboplatin affected the hearing of children with retinoblastoma., Methods: Children with retinoblastoma who were treated with intra-arterial carboplatin chemotherapy were included. Hearing tests before chemotherapy including tympanometry, distortion product otoacoustic emissions, and audiogram (if achievable) were performed and repeated 3 to 9 months after concluding intra-arterial therapy. The study was approved by the institutional review board. Patients were identified from the retinoblastoma clinic when the treatment plan included intra-arterial carboplatin chemotherapy. Children were excluded if they had previous intra-arterial carboplatin or preexisting hearing loss but were included if they had systemic carboplatin and dosing was available. Tympanometry was performed to rule out inner ear fluid. All examinations were performed by a certified audiologist with the same equipment, calibrated regularly by a certified technician., Results: Twenty-two children (32 eyes) were evaluable. Because most children are diagnosed at a young age and are unable to participate in an audiogram, distortion product otoacoustic emission measurement was the primary measurement. No child displayed hearing loss., Conclusions: Intra-arterial chemotherapy with carboplatin did not cause ototoxicity in any child by distortion product otoacoustic emission measurement in contrast to systemic chemotherapy where ototoxicity is common. Distortion product otoacoustic emission levels were essentially unchanged from before to after intra-arterial chemotherapy in children with retinoblastoma. These findings suggest that intra-arterial carboplatin does not affect outer hair cell function, and distortion product otoacoustic emission tests can provide useful information when monitoring children at risk of developing carboplatin ototoxicity. [ J Pediatr Ophthalmol Strabismus . 2025;62(1):27-32.] ., Competing Interests: Disclosure: The authors have disclosed no potential conflicts of interest, financial or otherwise.

Introduction: Extensive small cell lung cancer (ES-SCLC) are currently managed using first-line chemotherapy options, including atezolizumab (Atezo) plus etoposide and carboplatin (CE) or durvalumab (Durva) plus etoposide with either cisplatin (PE) or carboplatin (CE). However, a definitive distinction in therapeutic effects between Atezo and Durva in these regimens remains unestablished., Methods: We analyzed data from 100 patients diagnosed with ES-SCLC who received immune checkpoint inhibitors (ICIs) as first-line chemotherapy. Among them, 70 were administered Atezo + CE, 12 received Durva + PE, and 18 received Durva + CE. We assessed the efficacy of the two ICIs across various factors., Results: The progression-free survival (PFS) and overall survival (OS) did not significantly differ between Atezo + CE and Durva + CE/PE as first-line chemotherapy treatments for SCLC. We observed no significant differences in age, sex, performance status (PS), liver metastasis, bone metastasis, or platinum-based agent usage between the treatment cohorts. However, a marked improvement in PFS and OS was observed in the solitary patient with brain metastasis treated with Atezo + CE., Conclusion: The primary distinction between these treatments was observed in the management of patients with brain metastasis. The literature lacks comparative studies on the effects of first-line ICI treatment on the central nervous system, rendering our findings significant in clinical practice. Despite the retrospective nature of this study and the potential for various biases, we recommend the preferential use of Atezo + CE in patients with brain metastasis to potentially enhance prognosis., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Purpose: Unresectable pediatric low-grade gliomas (LGG) usually need adjuvant therapy, and carboplatin hypersensitivity reaction (HR) commonly leads to premature treatment cessation of a standard chemotherapy regimen. In the molecular era, advances in understanding tumor genetic characteristics allowed the development of targeted therapies for this group of tumors; however, cost-effectiveness assessment of treatments, especially in low-income countries, is crucial. The aim is to describe the results of carboplatin desensitization protocol in a single center in a middle-income country., Method: Prospective analysis of children with LGG submitted to carboplatin desensitization from December 2017 to June 2020 with follow-up until April 2024., Results: Nine patients were included. The mean age was 11 years. Five patients were male. Seven had optic pathway and two cervicomedullary location. Six had histologic diagnosis and four molecular analyses. The incidence of carboplatin reactions during the study period was 39.1%. Six patients underwent skin prick test, three with positive results. The first HR occurred, on average, around the 9th cycle of treatment. All patients had cutaneous symptoms, and five out of nine had anaphylaxis as the first reaction. 77.7% of the patients completed the protocol, and the clinical benefit rate (stable disease and partial response) was 88.8%. Six patients further required other lines of therapy. Monthly, the total cost for carboplatin was $409.09, and for target therapies (dabrafenib plus trametinib), $4929.28 to $5548.57., Conclusion: Our study presented an interesting and cost-effective option where desensitization allowed children with HR to be treated with first-line therapy, avoiding the discontinuation of an effective treatment., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the hospital’s Research Ethics Board IOP-GRAACC and UNIFESP (Federal University of Sao Paulo). Consent for publication: The study was approved by the hospital’s Research Ethics Board IOP-GRAACC and UNIFESP (Federal University of Sao Paulo). Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Gemcitabine plus cisplatin (GC) is a highly active and commonly used regimen in locally advanced/metastatic urothelial carcinoma (la/mUC). With GC, cisplatin is dosed at 70 mg/m 2 on day 1 of a 3-week cycle; however, for many patients, impaired renal or cardiac function, neuropathy, or poor performance status (PS) can preclude the use of cisplatin. A promising alternative is split-dose GC, in which the cisplatin dose is divided over 2 days., Methods: We conducted a systematic literature review (SLR) and network meta-analysis (NMA) to better understand treatment patterns and comparative effectiveness and safety of split-dose GC vs gemcitabine plus carboplatin (GCa), GC, and methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC)., Results: Among 120 identified studies, 16 studies representing 1,767 patients included split-dose GC. Common reasons for choosing split-dose GC were impaired renal function, age > 70 years, comorbidities, and physician preference. Split-dose GC had objective response rates (ORRs) of 39%-80%, median progression-free survival (PFS) of 3.5-9.9 months, and median overall survival (OS) of 8.5-18.1 months. Discontinuation rates due to adverse events were 5%-38%. In the NMA, ORR with split-dose GC was significantly higher than with GCa. PFS and OS for split-dose GC were similar to that observed with the other regimens (GCa, GC, and MVAC)., Conclusions: This is the first SLR and NMA of split-dose GC in la/mUC. Despite heterogeneity in the limited studies included, split-dose GC demonstrated comparable effectiveness and safety profile to those seen with other regimens. Split-dose GC thus has the potential to extend the la/mUC population eligible to receive cisplatin-based regimens and warrants further prospective study., Competing Interests: Disclosure Richard O'Dwyer has received support for travel and attending meetings from Pfizer and research funding from the healthcare business of Merck KGaA, Darmstadt, Germany. Mihaela G. Musat and Hoora Moradian are employees of Cytel, which was contracted for this work by the healthcare business of Merck KGaA, Darmstadt, Germany. Ioana Gulas and Elizabeth Hubscher were employees of Cytel at the time of the study. Silke Guenther was an employee of the healthcare business of Merck KGaA, Darmstadt, Germany, at the time of the study. Mairead Kearney is an employee of the healthcare business of Merck KGaA, Darmstadt, Germany. Srikala S. Sridhar has served in consulting or advisory roles for Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, Janssen, Merck & Co, Kenilworth, NJ, Pfizer, Roche/Genentech, and Seagen and has received institutional research funding from the healthcare business of Merck KGaA, Darmstadt, Germany., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In patients with early-stage triple-negative breast cancer, the phase 3 KEYNOTE-522 trial showed significant improvements in pathological complete response and event-free survival with the addition of pembrolizumab to platinum-containing chemotherapy. Here we report the final results for overall survival., Methods: We randomly assigned, in a 2:1 ratio, patients with previously untreated stage II or III triple-negative breast cancer to receive neoadjuvant therapy with four cycles of pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks plus paclitaxel and carboplatin, followed by four cycles of pembrolizumab or placebo plus doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide. After definitive surgery, patients received adjuvant pembrolizumab (pembrolizumab-chemotherapy group) or placebo (placebo-chemotherapy group) every 3 weeks for up to nine cycles. The primary end points were pathological complete response and event-free survival. Overall survival was a secondary end point., Results: Of the 1174 patients who underwent randomization, 784 were assigned to the pembrolizumab-chemotherapy group and 390 to the placebo-chemotherapy group. At the data-cutoff date (March 22, 2024), the median follow-up was 75.1 months (range, 65.9 to 84.0). The estimated overall survival at 60 months was 86.6% (95% confidence interval [CI], 84.0 to 88.8) in the pembrolizumab-chemotherapy group, as compared with 81.7% (95% CI, 77.5 to 85.2) in the placebo-chemotherapy group (P = 0.002). Adverse events were consistent with the established safety profiles of pembrolizumab and chemotherapy., Conclusions: Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab resulted in a significant improvement, as compared with neoadjuvant chemotherapy alone, in overall survival among patients with early-stage triple-negative breast cancer. (Funded by Merck Sharp and Dohme, a subsidiary of Merck [Rahway, NJ]; KEYNOTE-522 ClinicalTrials.gov number, NCT03036488.)., (Copyright © 2024 Massachusetts Medical Society.)

Background: Carboplatin (CBDCA) plus pemetrexed (PEM) is a commonly-used thoracic cancer treatment. As both CBDCA and PEM are excreted via the kidneys, renal impairment (RI) can lead to severe neutropenia, the most typical adverse event in the treatment. We aimed to determine the impact of baseline RI on the development of severe neutropenia following real-world CBDCA + PEM-containing treatments., Methods: Patients with thoracic cancer receiving CBDCA + PEM-containing treatments (n = 155) were divided into a control group (baseline creatinine clearance [CCr] ≥ 60 mL/min) and an RI group (baseline CCr < 60 mL/min) and retrospectively evaluated. The primary endpoint was the incidence of severe neutropenia during the first cycle. We also assessed factors associated with the development of severe neutropenia., Results: Severe neutropenia during the first cycle was confirmed in 41.2% of the patients in the RI group, which was significantly higher than that in the control group (20.7%, P = 0.02). Additionally, severe neutropenia during all evaluation periods was also more prevalent in the RI group compared to the control group (47.1% vs. 24.8%, P = 0.02). In contrast, the incidence of severe thrombocytopenia was not different. Multivariate logistic regression analyses identified RI as a risk factor for severe neutropenia (adjusted odds ratio 2.71; 95% confidence interval 1.18-6.21, P = 0.02 for the first cycle; 2.62, 1.17-5.84, P = 0.02 for all evaluation periods)., Conclusion: Our study revealed that patients with baseline RI exhibited severe neutropenia after CBDCA + PEM-containing treatments., Competing Interests: Declarations. Ethical approval: All procedures performed in this study involving human participants were performed in accordance with the ethical standards of the institutional and/or national research committee and the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. For this type of retrospective study, the need for formal consent was waived by the Ethical Review Board for Life Science and Medical Research at Hokkaido University Hospital. Consent to participate: Formal consent was not required for this type of retrospective study. Consent for publication: Not applicable. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Importance: Adjuvant therapy is an important and effective treatment for retinoblastoma. However, there is a lack of head-to-head clinical trials comparing 3 vs 6 cycles of CEV chemotherapy (carboplatin, etoposide, and vincristine) for enucleated unilateral retinoblastoma with high-risk pathological features., Objective: To assess whether 3 cycles of CEV chemotherapy is noninferior to 6 cycles for enucleated unilateral retinoblastoma with high-risk pathological features., Design, Setting, and Participants: This double-center, randomized, open-label, noninferiority trial was conducted at 2 premier eye centers in China and included 187 patients who had undergone enucleation for unilateral retinoblastoma with high-risk pathological features (massive choroidal infiltration, retrolaminar optic nerve invasion, or scleral infiltration) between August 2013 and March 2024. The final date of follow-up was March 21, 2024., Interventions: Patients were randomly assigned to receive either 3 (n = 94) or 6 (n = 93) cycles of CEV chemotherapy regimen after enucleation., Main Outcomes and Measures: The primary end point was disease-free survival, with a noninferiority margin of 12%. Secondary end points encompassed overall survival, safety, economic burden, and the quality of life of children., Results: All 187 patients (median [IQR] age, 25.0 [20.0-37.0] months; 83 [44.4%] female) completed the trial. Median (IQR) follow-up was 79.0 (65.5-102.5) months. Five-year disease-free survival was 90.4% for the 3-cycle group vs 89.2% for the 6-cycle group (difference, 1.2% [95% CI, -7.5% to 9.8%]), which met the noninferiority criterion (P = .003 for noninferiority). The 6-cycle group experienced a higher frequency of adverse events, greater reduction in quality of life scores, and increased costs compared with the 3-cycle group., Conclusions and Relevance: Among patients with unilateral pathologic high-risk retinoblastoma, 3 cycles of CEV chemotherapy resulted in 5-year disease-free survival that was noninferior to 6 cycles of CEV chemotherapy., Trial Registration: ClinicalTrials.gov Identifier: NCT01906814.

Background: Platinum-based antineoplastic drugs are widely used in the treatment of solid tumors. Carboplatin is a safe and efficacious adjuvant treatment for stage I seminoma following a risk-adapted treatment strategy. It consists in the administration of one or two courses for patients with one or both of rete testis involvement or tumor size more than 4 cm. Carboplatin is used with the purpose of minimizing nephrotoxicity and ototoxicity caused by cisplatin while achieving excellent results. We present a case of carboplatin-induced hematuria that led to an acute kidney injury as a rare complication., Case Presentation: A 48 year-old Caucasian man with no medical history and no history of renal disease presented with a painless testicular mass. He underwent an orchiectomy for stage I testicular seminoma and received one course of adjuvant carboplatin (area under the curve of 7); 2 days later, he developed frank hematuria associated with back pain. The physical examination revealed mild suprapubic tenderness and Goldflam's sign was positive bilaterally. Blood tests did not reveal anemia, his platelet count was normal, and creatinine levels were in range. Due to persisting hematuria requiring continuous bladder irrigation, he was hospitalized to monitor renal function and was initially managed conservatively with intravenous analgesics and adequate hydration. The following day, he developed an acute kidney injury (serum creatinine 1.90 mg/dL, glomerular filtration rate 41 mL/min/m 2 ). Transurethral cystoscopy showed a blood clot on the left urinary meatus, which was irrigated and removed, revealing a clear ureteral jet. With no further measures, creatinine started declining and back pain improved. His acute kidney injury resolved in the following 72 hours. Computed tomography urogram showed a left ureteral ectasia with an enhanced urothelium within the upper and middle ureter, suggesting ureteral obstruction. The patient improved completely and was discharged successfully. On further follow-up 2 months later, a computed tomography urogram showed a complete resolution of obstructive changes., Conclusions: Hematuria and acute kidney injury are rare but clinically relevant adverse events associated with the administration of carboplatin, regardless of the administered and accumulated dose. It is crucial to recognize this event and start adequate hydration promptly to prevent further kidney damage and the need for more aggressive measures, such as ureteral stenting or percutaneous nephrostomy., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Competing interests The authors declare that they have no competing interests., (© 2024. The Author(s).)

Objective: To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) in preventing neutropenia during concurrent radiotherapy combined with weekly chemotherapy in patients with cervical cancer., Methods: From September 2019 to November 2020, 180 patients with cervical cancer who required concurrent chemoradiotherapy (CCRT) were enrolled in this study. The patients were randomly divided into the following three groups at a ratio of 1:1:1: Group A (PEG-rhG-CSF), Group B (PEG-rhG-CSF + rhG-CSF) and the control group (rhG-CSF). Cisplatin or carboplatin was administered weekly. The primary endpoint was the incidence of grade 3/4 neutropenia. The secondary endpoints were the incidence of febrile neutropenia (FN), delay of radiotherapy, chemotherapy dose reduction, rate of PFS at 2 years and 3 years, and incidence of adverse reactions., Results: Sixty patients were randomly assigned to each group. Two patients in Group B withdrew from the trial for personal reasons. The incidence of grade 1/2 neutropenia in the Control group was significantly lower than that in Group A and Group B (P < 0.001). However, the incidence of grade 3/4 neutropenia in the Control group was significantly greater than that in Group A and Group B (P < 0.001). There was no significant difference in the incidence of FN among the three groups (P = 0.771). The rate of platinum dose reduction in Group A (6.7%) and Group B (5.2%) was significantly lower than that in the Control group (30.0%) (P < 0.001). The delay rate of radiotherapy in Group A (10%) and Group B (13.8%) was obviously inferior to that in the Control group (31.7%) (P = 0.006). The 2-year PFS rates of Group A, Group B, and the Control group were 93.3%, 98.3%, and 91.7%, respectively, with no statistically significant difference (P = 0.270). The 3-year PFS rates were 89.8%, 94.1%, and 84.9%, respectively, with no statistically significant difference (P = 0.178). No treatment-related serious adverse events occurred in any of the patients., Conclusion: In Group A and Group B, The prophylactic application of PEG-rhG-CSF during conventional chemoradiotherapy combined with weekly chemotherapy for patients with cervical cancer can reduce the incidence of grade 3/4 neutropenia and does not increase the incidence of adverse reactions when compared to Control group., Trial Registration: chictr.org.cn, ChiCTR1900026309, registered 29 September 2019-prospectively registered., Competing Interests: Declarations Ethics approval and consent to participate This study was approved by the Medical Ethics Committee of the Affiliated Cancer Hospital of Zhengzhou University (No. 2019221). All patients signed informed consent forms. Consent for publication The study received written informed consent for publication by all patients. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Karyomegalic interstitial nephritis (KIN) is a rare renal diagnosis associated with both genetic and medication etiologies. The primary gene associated with KIN is the FAN1 gene which encodes a protein responsible for DNA interstrand repair. Common medication triggers of KIN are chemotherapeutic agents, especially those which disrupt DNA structure such as carboplatin. Despite overlap between these mechanisms, it has not clearly been established if medication usage requires an underlying genetic predisposition for triggering KIN or if medications alone are sufficient. This ambiguous pathogenesis can make it difficult to appropriately assess risk of KIN development when starting patients on one of the known KIN-inducing therapies. Additionally, brentuximab vedotin, an antibody-drug conjugate directed against CD30, has not been previously implicated in KIN development., Case Presentation: We present a 49-year-old woman previously diagnosed with metastatic Hodgkin's lymphoma who was treated with doxorubicin, bleomycin, vinblastine, and dacarbazine, then 3 cycles of ifosfamide, carboplatin, etoposide, all of which were discontinued due to side effects. Following an episode of acute kidney injury, the serum creatinine was 1.09 mg/dL. She then received 2 doses of brentuximab, the serum creatinine rose, and the drug was discontinued. Kidney biopsy done 2 months after brentuximab and 5 months following ifosfamide therapies showed karyomegalic interstitial nephritis. Genetic evaluation showed no FAN1 gene mutations. The patient was started on pembrolizumab; no steroids were given due to concerns about interference with lymphoma immunotherapy. She remains with stable disease and stable chronic kidney disease., Conclusions: This case presents a patient who developed KIN with a progressively rising serum creatinine after ifosfamide, carboplatin and brentuximab treatment. Although ifosfamide and carboplatin have known associations with the development of KIN, this case raises the possibility that brentuximab, which has a different mechanism of action, also may be associated with KIN. Additionally, the genetic findings demonstrate that drug-induced KIN can develop in the absence of FAN1 mutations, a finding not previously reported., Competing Interests: Declarations Ethics approval and consent to participate This case report was reviewed and deemed not to need Institutional Review Board Approval at Cedars Sinai Medical Center. The patient has provided consent for genetic studies. Consent for publication Patient has given written informed consent for all information presented in this manuscript, including personal and clinical details, to be included and to be submitted as written. Competing interests None, (© 2024. The Author(s).)

Objectives: To assess the efficacy and toxicity of paclitaxel and carboplatin (PC) compared to bleomycin, etoposide, and cisplatin (BEP) for treatment of newly diagnosed Stage IIA-IV or recurrent chemotherapy-naive ovarian sex cord-stromal tumors (SCST)., Methods: This phase II noninferiority trial randomly assigned patients to receive PC (6 cycles P 175 mg/m2 and C AUC = 6 IV every 3 weeks), or BEP (4 cycles B 20 units/m2 IV push day 1, E 75 mg/m2 IV days 1-5, and cisplatin 20 mg/m2 IV days 1-5 every 3 weeks). The primary endpoint was progression- free survival (PFS). This trial is registered with ClinicalTrials.gov, NCT01042522., Results: At the interim analysis, 63 patients (31 PC and 32 B.P. had accrued between Feb 8, 2010 and Apr 30, 2020. Median age was 48 years. 87% had granulosa cell tumors. 37% had measurable disease. The DSMB closed accrual early for futility of PC arm. The futility analysis was supported by an estimated HR = 1.11 [95% CI: 0.57 to 2.13] which exceeded the pre-determined threshold for non-inferiority (1.10). Median PFS was 27.7 months [11.2 to 41.0] for PC and 19.7 months for BEP [95% CI: 10.4-52.7]. PC patients had fewer grade 3 or higher adverse events (PC 77% vs BEP 90%)., Conclusions: The study met its pre-specified criterion for stopping early for futility and so failed to demonstrate non-inferiority of PC versus BEP in ovarian SCSTs, in a non-inferiority test with a hazard ratio margin of 1.1. Both PC and BEP may be considered in patients with advanced/recurrent SCST., Competing Interests: Declaration of competing interest Dr. Brown has participated in the Speakers' Bureau for Clovis and for Eisai and has received funding for this. Dr. Brown has participated in Advisory Boards or as a consultant with AstraZeneca, Caris, Biodesix, Janssen, Tempus, Olympus, Clovis, Invitae, Verastem, and GSK/Tesaro. Dr. Brown has participated in research with GSK/Tesaro and Genentech. Dr. Austin Miller reports that his institution received payments for serving on a Data Safety Monitoring Board or Advisory Board for Agenus, AstraZeneca, VBL Therapeutics. Dr. Floor Backes reports research grants to Institution from Merck, Eisai, ImmunoGen, Clovis, Beigene, Natera, Tempus, AstraZeneca. Dr. Backes reports receiving personal fees from UptoDate. Dr. Backes reports receiving personal fees for serving on Advisory boards for Agenus, Merck, Clovis, Immunogen, Eisai, AstraZeneca, GlaxoSmithKline, Myriad, BioNTech and Daiichi Sankyo. Dr. Backes received honoraria for CME lectures from Clinical Educational Concepts, Clinical Care Options, Medscape/WebMD, Med Learning 13Health, CMR Institute, Global Learning Initiative/Prova, OncLive, Targeted Oncology and Research to Practice. GlaxoSmithKline provided Dr. Backes with support for travel. Dr. Backes served as a Board member for the Society of Gynecology Oncology (unpaid), Dr. Backes served as Co-Chair for NRG Oncology Developmental Therapeutics Committee as well as Co-Chair for IGCS Education 360. Dr. David Bender reports receiving grant support from Merck, Sharp & Dohme Company, Clovis Oncology, Inc. and Genentech. Dr. David Miller reports Grants to Institution from Advenchen, Forty Seven, Merck, Syros, US BIOTEST and Regeneron. He also reports receiving royalties from Karyopharm. Dr. Miller received consulting fees from Karyopharm, Incyte, Eisai, Merck, GlaxoSmithKline and Immunogen. Dr. Matthew Powell reports personally receiving consulting fees from GSK, Merck, Eisai, Seagen, Jazz, Clovis Oncology, AstraZeneca, Asdi Bioscience and AbbVie. He also reports participating on an Advisory Board for GSK and receiving compensation for the same. Additionally, Dr. Powell served in Leadership roles for SGO, NRG and GCSC and receiving compensation for the same. Dr. Westin has received research support to institution from AstraZeneca, Avenge Bio, Inc., Bayer, Bio-Path, Clovis Oncology, GSK, Jazz Pharmaceuticals, Mereo, Novartis, Nuvectis, Roche/Genentech, Zentalis. Dr. Westin has received consulting fees from AstraZeneca, Caris, Clovis Oncology, Eisai, EQRX, Gilead, GSK, Immunocore, ImmunoGen, Lilly, Merck, Mereo, Mersana, NGM Bio, Nuvectis, Roche/Genentech, SeaGen, Verastem, Vincerx, Zentalis and ZielBio. Dr. Bonebrake reports providing patients with diagnosis of stromal ovarian tumors. Additionally, Dr. Bonebrake reports participating on Advisory Board for Blueprint Medicine (no consulting fee received), Merck – Global Cervical and Ovarian Cancer Virtual Advisory Board (no consulting fee) and AstraZeneca – AZ eVOLVE DMC (ongoing). Dr. Bonebrake served on the Board of Directors for the GOG Foundation (unpaid) and reports receiving occasional travel reimbursement to attend meetings and NRG Oncology Board of Directors (unpaid). Dr. Muller reports grants to her Institution, New Mexico Minority Underserved NCORP) to support enrollment to all NCI NCTN trials. Dr. Muller also reports contracts to institution to enroll to GOG Partner trials from GOG Partners Foundation (Seagen, GSK, Mersana, Alkermes Inc., Merck, Verastem, Immunogen, etc.) as well as contracts to her Institution for enrollment to specific clinical trials, Linnaeus Therapeutics. Dr. Muller also reports serving as advisory on disparity advisory councils for GSK and Seagen to advise on ways to increase minority enrollment to clinical trials. Dr. Secord reports grants received to Institution from AbbVie, Aravive Inc., AstraZeneca, Clovis, Eisai, Ellipses, I-MAB Biopharma, GSK, Immunogen, Merck, Mersana OncoQuest/CanariaBio, Roche/Genentech, Seagen Inc., TapImmune, Tesaro/GSK, VBL Therapeutics. Dr. Secord reports personally receiving honoraria from @Point of Care, Clinical Care Options, Curio Science, PeerView, Bio ASCENT, RTP, GOG Foundation (Highlight reel) and GOG Foundation Symposium. Also, patents planned, issued or pending on “Blood based biomarkers in ovarian cancer” without compensation, She reports serving on Data Safety Monitoring Board or Advisory Board for AstraZeneca, Clovis, Gilead, Immunogen, Imvax, Merck, Mersana, Natera, Onconova and OncoQuest/Canariabio without compensation. Dr. Secord reports serving in leadership role for SGO (uncompensated), GOG (personal fee received), AAOGF (uncompensated) and NRG who provided grant to her institution. Finally, Dr. Secord receiving medical writing from AstraZeneca. Clinical Trial Steering Committees for the AXLerate trial (Aravive), AtTEnd trial (Hoffman-LaRoche), Oval Trial (VBL Therapeutics), FLORA-5 trial (CanariaBio), and QPT-ORE-004 (CanariaBio), all without compensation. Dr. Crane reports serving on the Speakers Bureau for Merck and GlaxoSmithKline but the relationship for each of these has been terminated. Dr. Crane served on the Advisor Board for both AstraZeneca and GlaxoSmithKline. Dr. Schorge reports receiving Williams Gynecology royalties from McGraw-Hill and royalties for 2 articles from UpToDate. Dr. Schorge also reports receiving Consulting fees from Best Doctors. Dr. Tew reports receiving consulting fees from UpToDate and honoraria for the Chemotherapy Foundation Symposium 2022. Dr. Sood reports NCI grant received relative to this study as well as receiving the American Cancer Society Research Professor Award. Dr. Sood reports consulting fees received from KIYATEC, ImmunoGen, Merck & Co, Lyon, GSK, AstraZeneca and Onxeo. He also reports patents planned issued or pending for the EGFL6 antibody. Dr. Sood participated on an Advisory Board for Advenchen and has stock in Bio-Path Holdings. Dr. Bookman reports serving on a DMC for Immunogen as well as an Advisory Board for Clovis, and his institution received payment for both. Dr. Aghajanian reports Clinical trial funding to Institution (MSK) from AbbVie – MSK PI, GOG3005; AstraZeneca – MSK PI, SOLO1/GOG 3004; National Coordinating Investigator & MSK PI, D081RC00001; ENGOT-ov6; AGO-OVAR 23; GOG-3025; Clovis – MSK PI, Ariel 2 & 3 and Genentech/Roche-MSK PI, GOG3015 (1Magyn050). Dr. Gershenson reports grants received from Novartis to his Institution. He also reports royalties personally received from Elsevier and UpToDate. Dr. Gershenson also received consulting fees from Verastem and Genentech. Dr. Gershenson also reports personal fees received for serving on the Advisory Boards for Aadi, Verastem and Beigene/Springworks. He received no compensation for serving as Chair, International Consortium for Low-Grade Serous Ovarian Cancer and reports stock ownership for Bristol Myers Squib, Johnson & Johnson and Procter and Gamble. The following Coauthors have no conflicts of Interest to disclose: Dr. Holman and Dr. Nagel., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: We evaluated the feasibility of completing 6 cycles of nab-paclitaxel (nab-P) and carboplatin (C) in a single arm prospective clinical trial for advanced/recurrent EC and safety and efficacy of day (D) 1, 8 nab-P in combination with D1 C q3weeks., Methods: Patients with early-stage, high-risk, advanced primary/recurrent EC without prior platinum/taxane exposure were enrolled in an open-label, single-institution trial (NCT02744898). Patients received 6 cycles of D1 nab-P 100 mg/m 2 IV with C AUC 6 IV and D8 nab-P 100 mg/m 2 IV q21D. The trial tested the null hypothesis that subjects completing 6 cycles was ≤0.50 versus the alternative that the proportion is ≥0.75 in a single stage design with alpha = 0.05 and power = 80% with 23 subjects. Patients who completed 6 cycles (primary outcome), objective response rate (ORR) and clinical benefit rate (CBR) were estimated with exact 95% Clopper-Pearson confidence intervals. Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods., Results: From 08/2016-03/2018, 23 patients were enrolled. Nineteen patients (82.6%, 95% CI: 61.2%, 95.0%) completed 6 cycles, thus we could reject our null. Twelve patients (52.2%) experienced ≥1 grade 3/4 treatment-related adverse events including: anemia, 6 (26.1%); neutropenia, 5 (21.7%); diarrhea, 3 (13.0%). Fourteen patients (60.1%) reported grade 1 neuropathy. Of 9 patients with measurable target lesions, the ORR was 33.3% (95% CI: 7.5%, 70.1%) and CBR was 55.6% (95% CI: 21.2%, 86.3%). Median PFS in the advanced/recurrent patients was 23.2 (95% CI: 12.1, NR) months., Conclusions: The nab-P/C D1, 8 regimen met pre-specified feasibility criteria with acceptable toxicity and efficacy. Use of nab-P decreases need for steroid pre-medications, and this carboplatin doublet may prove advantageous for trials assessing combinations with immune checkpoint inhibitors in advanced EC., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Objective: This study compared the effectiveness, safety, and tolerability of dose-dense paclitaxel and carboplatin plus bevacizumab (ddTC+Bev) with ddTC for advanced ovarian cancer., Methods: We retrospectively analyzed the clinical records of 134 patients who received ddTC+Bev or ddTC as first-line chemotherapy for stage III-IV ovarian cancer. Progression-free survival as primary endpoint of this study was compared using the log-rank test. Cox proportional hazards model and propensity score matching (PSM) were used to analyze prognostic factors, and the frequency of adverse events was examined using the χ² test., Results: We categorized 134 patients in the ddTC+Bev (n=57) and ddTC (n=77) groups who started treatment at four related institutions from November 2013 to December 2017. No patients used poly (ADP-ribose) polymerase inhibitors as the first line maintenance therapy. The progression-free survival (PFS) of the ddTC+Bev group had a significantly better prognosis than that of the ddTC group (hazard ratio [HR]=0.50; 95% confidence interval [CI]=0.32-0.79; p<0.003). Multivariate analysis showed that ddTC+Bev regimen was a prognostic factor. However, intergroup comparison using PSM revealed that the PFS of the ddTC+Bev group had a nonsignificantly better prognosis than that of the ddTC group (HR=0.70; 95% CI=0.41-1.20; p=0.189). Few adverse events above G3 were noted for ddTC+Bev, which were sufficiently tolerable., Conclusion: This study could not demonstrate that adding Bev to ddTC improves prognosis. Further studies with more cases are warranted., Competing Interests: Aikou Okamoto has honoraria from Takeda Pharmaceutical Company Ltd., AstraZeneca K.K., MSD K.K., Mochida Pharmaceutical Co., Ltd., Bayer Holding Ltd., Kaken Pharmaceutical Co., Ltd., ASKA Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Kissei Pharmaceutical Co., Ltd., Fuji Pharma Co., Ltd., Zeria Pharmaceutical Co., Ltd., Eisai Co., Ltd., and Takeda Pharmaceutical Company Ltd. Also, Dr. Okamoto was supported by research funding from Meiji Holdings Co., Ltd., Fuji Pharma Co., Ltd., Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Kaken Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., ASKA Pharmaceutical Co., Ltd., Mochida Pharmaceutical Co., Ltd., MSD K.K., Eisai Co., Ltd., Takeda Pharmaceutical Company Ltd., Mochida Pharmaceutical Co., Ltd, Linical Co., Ltd., Pfizer Japan Inc., Gyne Mom Co.Ltd, Terumo Corporation, Kissei Pharmaceutical Co., Ltd., AstraZeneca K.K., Tsumura & Co., and Daiichi Sankyo Co., Ltd., (© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Background: Neoadjuvant chemotherapy may be considered for patients with ovarian cancer (OC) whose tumors are deemed unlikely to be completely cytoreduced to no gross residual disease (R0) or who are poor surgical candidates. This Ib/II study was designed to assess the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus carboplatin as neoadjuvant chemotherapy for stages III-IV, unresectable OC., Methods: Eligible patients with stage III-IV, unresectable OC were enrolled in this phase Ib/II study. All patients received neoadjuvant nab-paclitaxel (260 mg/m 2 , day 1, every 3 weeks) plus carboplatin (AUC 5, day 1, every 3 weeks) for 3 cycles before surgery, followed by 3-6 cycles of adjuvant chemotherapy. The phase Ib primary endpoint was safety; the phase II primary endpoint was the R0 resection rate. Secondary endpoints were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety (for all populations)., Results: Sixty-two patients were enrolled and were given neoadjuvant therapy treated between October 2019 and December 2020, of whom 9 were in the phase Ib portion and 53 in the phase II portion. A total of 53 patients underwent surgery with an R0 resection rate of 73.6% (95% CI, 59.7-84.7%). With a median follow-up of 17.5 (range 0.7-36.7) months, for all patients, the best ORR was 83.9% (95% CI, 71.7-92.4%) with 47 partial responses, the median PFS was 18.6 (95% CI, 13.8-23.3%) months, and median OS was not reached. During the neoadjuvant chemotherapy, treatment-related adverse events (TRAEs) of any grade occurred in 91.9% (57/62) of all patients. The most common hematologic TRAEs were neutropenia (55/62, 88.7%), and non-hematologic toxicity was alopecia (36/62, 58.1%). Forty-nine patients (79.0%) experienced at least one grade 3-4 TRAEs, with the most common was neutropenia (44/62, 71.0%). Besides, delays in neoadjuvant chemotherapy and surgery due to AEs were observed in 9 (1 in phase Ib; 8 in phase II) and 7 (phase II) patients, respectively., Conclusions: The study demonstrated an encouraging efficacy and manageable safety profile of neoadjuvant chemotherapy nab-paclitaxel plus carboplatin in stage III-IV, unresectable OC. In addition, AEs resulting in chemotherapy and surgery delays should be cautiously considered in this clinical setting., Trial Registration: ClinicalTrials.gov, ChiCTR1900026893. Registered at 25 October 2019., (© 2024. The Author(s).)

Background: Despite promising outcomes of treatment with anti-programmed cell death (PD)-1/PD-ligand (L)1 agents in combination with platinum-doublet chemotherapy (PDC) in the first-line setting, a significant unmet medical need remains in patients with PD-L1-unselected non-small cell lung cancer (NSCLC)., Methods: This multicenter, open-label, phase 1b study comprising dose-confirmation and dose-expansion parts investigated the combination of spartalizumab and various PDC regimens, with or without canakinumab, in treatment-naïve patients with PD-L1-unselected, metastatic NSCLC. The primary objectives were to determine maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) of spartalizumab, with or without canakinumab, in combination with PDC in the dose-confirmation part and antitumor activity of spartalizumab in the dose-expansion part., Results: The MTD/RDE of spartalizumab was 300 mg every 3 weeks (Q3W) when administered with either gemcitabine (1250 mg/m 2 )/cisplatin (75 mg/m 2 ) (group A; no dose-limiting toxicities [DLTs]), pemetrexed (500 mg/m 2 )/cisplatin (group B; 2 DLTs: grade 2 posterior reversible encephalopathy syndrome and grade 4 hyponatremia), or paclitaxel (200 mg/m 2 )/carboplatin area under the curve 6 min*mg/mL (group C; 1 DLT: grade 4 neutropenic colitis). The RDE of canakinumab combined with spartalizumab and pemetrexed/cisplatin (group E; no DLTs) was 200 mg Q3W (no dose-expansion part was initiated). No new safety signals were identified. In groups A, B, C, and E, the overall response rates were 57.6%, 55.3%, 51.5%, and 57.1%, respectively. Group B compared with other groups had the longest median progression-free survival (10.4 months vs. 6.2-7.5 months), overall survival (29.7 months vs. 16.1-21.0 months), and duration of response (30.1 months vs. 6.0-8.2 months)., Conclusions: The combination of spartalizumab and PDC, with or without canakinumab, was well tolerated across treatment groups. The antitumor activity across treatment groups was comparable with that of pembrolizumab and pemetrexed combination. Canakinumab did not appear to improve the antitumor activity when combined with spartalizumab, pemetrexed and cisplatin., Trial Registration: The trial was registered in Clinicaltrials.gov with identifier no. NCT03064854. Date of Registration: 06 February 2017., (© 2024. The Author(s).)

Objectives: Certain guidelines recommend caution when administering immunotherapy in patients with pre-existing interstitial lung disease (ILD) owing to the high incidence of pneumonitis induced by anti-cancer therapy. A prospective clinical trial assessing the safety of chemoimmunotherapy in patients with small-cell lung cancer (SCLC) and pre-existing ILD is warranted. Therefore, this study evaluated the safety and efficacy of chemoimmunotherapy in patients with extensive-stage (ES)-SCLC and mild idiopathic interstitial pneumonia (IIP)., Methods: In this multicenter prospective trial, patients with ES-SCLC and pre-existing mild chronic fibrosing IIP were recruited. Mild IIP was defined as the exclusion of poor pulmonary function, a definite usual interstitial pneumonia (UIP) pattern, and positivity for autoantibodies in blood tests. The patients received durvalumab, etoposide, and carboplatin every three weeks (induction phase), followed by 1,500 mg durvalumab every four weeks (maintenance phase). The primary endpoint was severe pneumonitis-free rate., Results: Twenty-one patients were included in the analysis. Among them, 13 patients displayed a probable UIP pattern, whereas eight patients exhibited an indeterminate for UIP pattern. Two patients (9.5 %) had pneumonitis of any grade during the induction phase; one had Grade 1 and the other had Grade 5 pneumonitis. No other patient developed pneumonitis during the maintenance phase. The severe pneumonitis-free rate was 95.2 % (95 % confidence interval (CI): 77.3-99.2 %). The median progression-free survival was 5.5 months (95 % CI: 3.6-6.4 months). Median overall survival was 10.7 months (95 % CI: 6.0 months to not reached)., Conclusions: Chemoimmunotherapy is a feasible treatment approach for patients with ES-SCLC and mild IIP., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Daichi Fujimoto reports financial support provided by AstraZeneca K.K. Ryota Shibaki received personal fees from AstraZeneca KK, Taiho Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., and MSD KK outside the submitted work. Daichi Fujimoto received grants from AstraZeneca K.K. during the study and personal fees from AstraZeneca KK, Boehringer Ingelheim Japan Inc., Ono Pharmaceutical Co. Ltd., Bristol-Myers Squibb Co. Ltd., Taiho Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., MSD KK, Eli Lilly Japan KK, Kyowa Kirin Co. Ltd., Janssen Pharmaceutical KK, Daiichi Sankyo Co. Ltd., Takeda Pharmaceutical Co. Ltd., and Novartis Pharma KK outside of the submitted work. Eisaku Miyauchi received personal fees from AstraZeneca KK, Boehringer Ingelheim Japan Inc., Ono Pharmaceutical Co. Ltd., Bristol-Myers Squibb Co. Ltd., Taiho Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., MSD KK, Eli Lilly Japan KK, Kyowa Kirin Co. Ltd., Daiichi Sankyo Co. Ltd., Takeda Pharmaceutical Co. Ltd., Merck Biopharma Co. Ltd., Pfizer Inc., Eisai Co. Ltd., Otsuka Pharmaceutical Co. Ltd., Amgen Inc., Thermo Fisher Scientific KK, Nippon Kayaku Co. Ltd., Sysmex Co. Ltd., KYORIN Pharmaceutical Co. Ltd., and Novartis Pharma KK outside the submitted work. Yoko Tsukita received personal fees from AstraZeneca KK, Bristol-Myers Squibb Co. Ltd., Taiho Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., MSD KK, Eli Lilly Japan KK, Daiichi Sankyo Co. Ltd., Eisai Co. Ltd., and Boehringer Ingelheim Japan Inc. outside the submitted work. Daisuke Arai has received personal fees from AstraZeneca KK, Taiho Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., MSD KK, Eli Lilly Japan KK, Ono Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., Merck, and Nippon Kayaku Co. outside the submitted work. Yoshihiko Sakata received personal fees from AstraZeneca KK, Amgen, Boehringer Ingelheim Japan Inc., Bristol-Myers Squibb Co. Ltd., Taiho Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., MSD KK, Eli Lilly Japan KK, Kyowa Kirin Co. Ltd., Takeda Pharmaceutical Co., Ltd., and Novartis Pharma KK outside the submitted work. Naoki Shingu received personal fees from AstraZeneca KK, Chugai Pharmaceutical Co. Ltd., Bristol-Myers Squibb Co. Ltd., Takeda Pharmaceutical Co. Ltd., and MSD KK outside the submitted work. Takashi Kijima received personal fees from Chugai Pharmaceutical Co. Ltd. outside the submitted work. Go Saito received personal fees from AstraZeneca KK, Taiho Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., MSD KK, Ono Pharmaceutical Co. Ltd., Pfizer, Daiichi Sankyo Company, and Novartis Pharma KK outside the submitted work. Yuki Sato received personal fees from AstraZeneca KK, Ono Pharmaceutical Co. Ltd., Bristol-Myers Squibb Co. Ltd., Taiho Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., MSD KK, Eli Lilly Japan KK, Kyowa Kirin Co. Ltd., Daiichi Sankyo Co. Ltd., and Takeda Pharmaceutical Co. Ltd., Pfizer Inc., Nippon Kayaku Co., Ltd., and Novartis Pharma KK outside the submitted work. Shinya Sakata received personal fees from AstraZeneca KK, Taiho Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., and Takeda Pharmaceutical Co. Ltd. outside the submitted work. Yoshihiko Taniguchi received personal fees from AstraZeneca KK, Bristol-Myers Squibb Co. Ltd., and Chugai Pharmaceutical Co. Ltd. outside the submitted work. Akito Hata has received personal fees from AstraZeneca KK, Taiho Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., Eli Lilly Japan KK, Pfizer Inc., and Boehringer Ingelheim outside the submitted work. Hirotaka Matsumoto received personal fees from AstraZeneca KK, Taiho Pharmaceutical Co. Ltd., Chugai Pharmaceutical Co. Ltd., MSD KK, Takeda Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., Ono Pharmaceutical Co. Ltd., and Boehringer Ingelheim outside the submitted work. Nobuyuki Yamamoto has received personal fees from AstraZeneca KK, Chugai Pharmaceutical Co. Ltd., MSD KK, Ono Pharmaceutical Co. Ltd., Daiichi Sankyo, Taiho Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co. Ltd., Boehringer Ingelheim Japan Inc., Pfizer Inc., Amgen Inc., Janssen Pharmaceutical KK, Terumo, Eli Lilly Japan KK, Novartis Pharma KK, Merck Biopharma, Guardant Health Japan, Accuray Inc., AbbVie, Kyorin Pharmaceutical Co. Ltd., Tsumura & Co., and Miyarisan Pharmaceutical outside the submitted work. Other authors declare that they have no competing financial interests or personal relationships that could have influenced the work reported in this study.]., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Atezolizumab, carboplatin, and etoposide (ACE) therapy is a standard of care for extensive-disease small cell lung cancer (SCLC); however, its safety data are scarce, limiting generalization to the Japanese population., Methods: This study aimed to compare the safety of ACE versus carboplatin and etoposide (CE) therapies in Japanese patients using the Diagnosis Procedure Combination (DPC) database by comparing the incidence of adverse events (AEs). Retrospective data on clinical background and AEs were extracted from the DPC database. Incidence rates and restricted mean survival times (RMSTs) up to 6 months were analyzed for 19 clinically important AEs. Covariates were adjusted using the inverse probability weighting method., Results: A total of 330,774 patients were identified using the International Statistical Classification of Diseases and Related Health Problems 10th Revision codes, of whom 277 were included in the ACE cohort and 478 in the CE cohort. Among the 19 AEs, the incidence of skin disorder and thyroid dysfunction was significantly higher in the ACE cohort compared with the CE cohort. The adjusted incidence rate ratios were 2.38 (95% confidence interval [CI] 1.04-5.43) for skin disorder and 6.92 (95% CI 2.00-23.89) for thyroid dysfunction. The adjusted RMST differences were - 8.2 days (95% CI - 16.0 to - 0.4 days) for skin disorder and - 8.8 days (95% CI - 15.7 to - 1.9 days) for thyroid dysfunction., Conclusions: This study provides evidence regarding the safety of ACE combination therapy in Japanese clinical practice using the DPC database, with results comparable to those reported in pivotal clinical trials., Trial Registration: UMIN Clinical Trials Registry ID UMIN000041508., (© 2024. The Author(s).)

Introduction: Atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) combination therapy is a standard of care for advanced non-squamous non-small cell lung cancer (NSQ-NSCLC); however, the lack of safety data limits its clinical application in Japan., Methods: This study compared the safety of ABCP with that of bevacizumab, carboplatin, and paclitaxel (BCP) combination for the treatment of advanced NSQ-NSCLC in Japanese patients by evaluating the clinical background and incidence of adverse events (AEs) based on data extracted from the Diagnosis Procedure Combination (DPC) database. Incidence rates and restricted mean survival times (RMSTs) for up to 1 year were analyzed for 19 clinically important AEs. Covariates were adjusted using the inverse probability weighting method., Results: A search conducted using the International Statistical Classification of Diseases and Related Health Problems 10th Revision codes identified 350,987 patients, of whom 202 were included in the ABCP cohort and 232 in the BCP cohort. Among the 19 AEs, the incidence of skin disorder and febrile neutropenia (FN) was significantly higher in the ABCP cohort versus the BCP cohort. The adjusted incidence rate ratios were 2.65 [95% confidence interval (CI) 1.43-4.91] for skin disorder and 1.70 (95% CI 1.01-2.85) for FN. The adjusted RMST differences were - 64.2 days (95% CI - 93.0 to - 35.4 days) and - 46.0 days (95% CI - 73.5 to - 18.5 days) for skin disorder and FN, respectively. These results were comparable to those of other pivotal clinical trials., Conclusions: The findings of this DPC database study highlight the safety of ABCP in Japanese clinical practice, and this methodology may facilitate more efficient research in real-world settings., Trial Registration: UMIN Clinical Trials Registry ID UMIN000041507., (© 2024. The Author(s).)

Importance: Outcomes for patients with unresectable stage III non-small cell lung cancer (NSCLC) treated with chemoradiation therapy (CRT) have improved with adjuvant immune checkpoint inhibitors, with a reported 5-year overall survival benefit of approximately 10% for adjuvant durvalumab vs placebo after completion of CRT without progression and with preserved performance status. Starting atezolizumab prior to CRT may allow more patients to benefit from immunotherapy., Objective: To evaluate clinical outcomes of patients treated with atezolizumab before and after CRT for unresectable stage III NSCLC., Design, Setting, and Participants: This single-cohort, phase II, nonrandomized controlled trial was conducted at 11 US sites. Patients with pathologically confirmed, unresectable stage III NSCLC who were treatment naive and had good performance status were enrolled between January 3, 2018, and July 24, 2019. Data were locked on March 21, 2023., Interventions: Patients received four 21-day cycles of atezolizumab, 1200 mg intravenously, with therapy administered on day 1 of each cycle. Patients not experiencing tumor progression continued to CRT (60 Gy to involved fields) concurrent with weekly carboplatin area under the curve of 2 and paclitaxel, 50 mg/m2, followed by planned consolidation carboplatin area under the curve of 6 and paclitaxel, 200 mg/m2, for two 21-day cycles. Patients not experiencing progression continued atezolizumab, 1200 mg, every 21 days to complete 1 year of therapy., Main Outcomes and Measures: The primary end point was the disease control rate at 12 weeks. Secondary end points were progression-free survival, overall survival, overall response rate, safety, and translational science end points., Results: A total of 62 patients (median [range] age, 63.9 [38.1-86.5] years; 32 female [51.6%]) were enrolled and received at least 1 dose of atezolizumab. The disease control rate at 12 weeks was 74.2% (80% CI, 65.7%-81.4%). Median progression-free survival was 30.0 months (95% CI, 15.8 to not evaluable), and the median overall survival was not reached. The overall survival rate at 24 months was 73.7% (95% CI, 63.4%-85.7%), and the overall response rate was 66.2%. Seventeen patients (27.4%) experienced grade 3 or higher immune-related adverse events, including 1 with grade 5 pneumonitis and 1 with grade 4 Guillain-Barré syndrome. Thirty patients (48.4%) experienced grade 3 or higher treatment-related adverse events., Conclusions and Relevance: These findings suggest that neoadjuvant atezolizumab merits further study based on safety and encouraging outcomes., Trial Registration: ClinicalTrials.gov Identifier: NCT03102242.

Background: Thymic carcinoma (TC) is a rare tumor with aggressive behavior. Chemotherapy with carboplatin plus paclitaxel represents the treatment of choice for advanced disease. Antiangiogenic drugs, including ramucirumab, have shown activity in previously treated patients. The RELEVENT trial was designed to evaluate the activity and safety of ramucirumab plus chemotherapy as first-line treatment in advanced TC., Patients and Methods: This phase II trial was conducted within the Italian TYME network. Eligible patients had treatment-naïve advanced TC. They received ramucirumab, carboplatin and paclitaxel for six cycles, followed by ramucirumab maintenance until disease progression or intolerable toxicity. Primary endpoint was objective response rate (ORR) according to RECIST v1.1 as assessed by the investigator. Secondary endpoints were progression-free survival (PFS), overall survival (OS) and safety. Centralized radiologic review was carried out., Results: From November 2018 to June 2023, 52 patients were screened and 35 were enrolled. Median age was 60.8 years, 71.4% of patients were male and 85.7% had Masaoka-Koga stage IVB. The Eastern Cooperative Oncology Group performance status was 0 in 68.5% and 1 in 31.4% of patients. At the present analysis carried out some months after the interim analysis (earlier than expected) on 35 patients, ORR was 80.0% [95% confidence interval (CI) 63.1% to 91.6%]. At the centralized radiological review of 33/35 assessable patients, ORR was 57.6% (95% CI 39.2% to 74.5%). After a median follow-up of 31.6 months, median PFS was 18.1 months (95% CI 10.8-52.3 months) and median OS was 43.8 months (95% CI 31.9 months-not reached). Thirty-two out of 35 patients (91.4%) experienced at least one treatment-related adverse event (AE), of which 48.6% were AE ≥ grade 3., Conclusions: In previously untreated advanced TC, the addition of ramucirumab to carboplatin and paclitaxel showed the highest activity compared to historical controls, with a manageable safety profile. Despite the small number of patients, given the rarity of the disease, the trial results support the consideration of this combination as first-line treatment in TC., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Chemotherapy-induced nausea and vomiting (CINV) is one of the adverse events that most affects oncologic patients' quality of life. Carboplatin AUC ≥ 4 belongs to agents with high emetic risk (moderate risk in ASCO guidelines). We aimed to compare the effectiveness of netupitant/palonosetron and dexamethasone triple combination (TC) therapy versus ondansetron and dexamethasone double combination (DC) therapy as antiemetic prophylaxis in patients with carboplatin AUC ≥ 4. As a secondary endpoint, in TC group we evaluated the effectiveness of changing NEPA administration timing from 1 h to 15 min before chemotherapy., Methods: Open-label prospective study conducted in a tertiary-care hospital in patients receiving carboplatin AUC ≥ 4. CINV was evaluated using MASCC antiemetic tool, in acute (<24 h) and delayed phase (24-120 h). Results were analyzed using χ 2 test., Results: Two-hundred four completed questionnaires (CQ) were analyzed (76 in DC and 128 in TC). The proportion of patients who remained emesis-free was superior for TC-treated group compared to DC, either in acute (99.2% vs 92.1%, p  = 0.0115) and delayed phase (97.6% vs 90.7%, p  = 0.043). Likewise, a higher proportion of TC-treated patients compared to DC remained nausea-free for the first 24 h after treatment (90.6% vs 71%, p  = 0.0004) and between 24 and 120 h (82.3% vs 62.7%, p  = 0.0025). The change of NEPA administration time showed similar effectiveness in terms of CINV control (81.6% vs 74.5%, p  = 0.70)., Conclusions: TC showed superiority in early and delayed CINV control in carboplatin AUC ≥ 4 regimens, with no significant differences among cancer types. Change in NEPA administration timing has beneficial implications; it allows NEPA to be administered at hospitals before chemotherapy session., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: High dose rate (HDR) image-guided brachytherapy with Cobalt-60 isotope is a relatively recent approach. The aim of the study is to evaluate the clinical and dosimetric parameters in terms of tumour response, bladder, and rectal toxicity in patients undergoing Co-60 HDR brachytherapy., Materials and Method: All patients were initially treated with chemoradiation (CT-RT) at our center or other referral centers with external beam radiation therapy (EBRT) for a dose of 45 Gy-60 Gy at 1.8-2Gy/fraction (including nodal boost) with concomitant chemotherapy with either cisplatin or carboplatin. Patients were then scheduled for brachytherapy within 1 week after completion of CT-RT and are assessed by local examination. Depending on local examination parameters at the time of brachytherapy they were eligible either for intracavitary brachytherapy (ICBT) or interstitial brachytherapy (ISBT)., Results: The complete response (CR) observed in stage I, II, III, IVA were 60%, 79.4%, 86% and 76.2% respectively. Complete response was seen in patients with mean EQD2 of 78.67 Gy 10 , 83.33 Gy 10 , 84.23 Gy 10 , 85.63 Gy 10 in stages I, II, III, IVA respectively. 79.2% of cisplatin-treated patients and 87.5% of carboplatin-treated patients had a complete response indicating that patients treated with either chemotherapy had similar response rates., Conclusions: According to results obtained from the study we conclude by saying that higher rates of complete response to treatment in cervical cancer is seen in patients with shorter overall treatment time (OTT), shorter interval between end of definitive CT-RT and beginning of brachytherapy and squamous cell histology. The study also noted the trend of increasing mean EQD2 to tumor with increasing stage for achieving complete response. Higher acute bladder and rectal toxicity is seen in patients who received EQD2 of ¿70-90Gy 3 and ¿70Gy 3 respectively. The study findings suggest that the clinical outcomes and the toxicities are clinically comparable with other radioisotope based HDR brachytherapy treatment., Competing Interests: The authors declare there are no competing interests., (©2024 Makkapati et al.)

Importance: For patients with non-small cell lung cancer whose disease progressed while receiving EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy, particularly third-generation TKIs, optimal treatment options remain limited., Objective: To compare the efficacy of ivonescimab plus chemotherapy with chemotherapy alone for patients with relapsed advanced or metastatic non-small cell lung cancer with the epidermal growth factor receptor (EGFR) variant., Design, Setting, and Participants: Double-blind, placebo-controlled, randomized, phase 3 trial at 55 sites in China enrolled participants from January 2022 to November 2022; a total of 322 eligible patients were enrolled., Interventions: Participants received ivonescimab (n = 161) or placebo (n = 161) plus pemetrexed and carboplatin once every 3 weeks for 4 cycles, followed by maintenance therapy of ivonescimab plus pemetrexed or placebo plus pemetrexed., Main Outcomes and Measures: The primary end point was progression-free survival in the intention-to-treat population assessed by an independent radiographic review committee (IRRC) per Response Evaluation Criteria in Solid Tumors version 1.1. The results of the first planned interim analysis are reported., Results: Among 322 enrolled patients in the ivonescimab and placebo groups, the median age was 59.6 vs 59.4 years and 52.2% vs 50.9% of patients were female. As of March 10, 2023, median follow-up time was 7.89 months. Median progression-free survival was 7.1 (95% CI, 5.9-8.7) months in the ivonescimab group vs 4.8 (95% CI, 4.2-5.6) months for placebo (difference, 2.3 months; hazard ratio [HR], 0.46 [95% CI, 0.34-0.62]; P < .001). The prespecified subgroup analysis showed progression-free survival benefit favoring patients receiving ivonescimab over placebo across almost all subgroups, including patients whose disease progressed while receiving third-generation EGFR-TKI therapy (HR, 0.48 [95% CI 0.35-0.66]) and those with brain metastases (HR, 0.40 [95% CI, 0.22-0.73]). The objective response rate was 50.6% (95% CI, 42.6%-58.6%) with ivonescimab and 35.4% (95% CI, 28.0%-43.3%) with placebo (difference, 15.6% [95% CI, 5.3%-26.0%]; P = .006). The median overall survival data were not mature; at data cutoff, 69 patients (21.4%) had died. Grade 3 or higher treatment-emergent adverse events occurred in 99 patients (61.5%) in the ivonescimab group vs 79 patients (49.1%) in the placebo group, the most common of which were chemotherapy-related. Grade 3 or higher immune-related adverse events occurred in 10 patients (6.2%) in the ivonescimab group vs 4 (2.5%) in the placebo group. Grade 3 or higher vascular endothelial growth factor-related adverse events occurred in 5 patients (3.1%) in the ivonescimab group vs 4 (2.5%) in the placebo group., Conclusions: Ivonescimab plus chemotherapy significantly improved progression-free survival with tolerable safety profile in TKI-treated non-small cell lung cancer., Trial Registration: ClinicalTrials.gov Identifier: NCT05184712.

A 73-year-old man with lung squamous cell carcinoma was administered carboplatin + nab-paclitaxel + pembrolizumab for four cycles. Subsequently, he presented with multiple purpuras on his extremities, joint swelling on his fingers, abdominal pain, and diarrhea, accompanied by acute kidney injury (AKI), increased proteinuria, hematuria, and elevated C-reactive protein levels. Skin biopsy showed leukocytoclastic vasculitis as well as IgA and C3 deposition in the vessel walls. Based on these findings, the patient was diagnosed with IgA vasculitis as an immune-related adverse event (irAE) induced by carboplatin + nab-paclitaxel + pembrolizumab. After discontinuation of pembrolizumab and glucocorticoids, the symptoms immediately resolved. Regular monitoring of skin, blood tests, and urinalysis are necessary, and the possibility of irAE IgA vasculitis should be considered in cases of purpura and AKI during treatment with immune checkpoint inhibitors., Competing Interests: AM has received honoraria from AstraZeneca, Nippon Kayaku, Merck, Kyowa Kirin, and Pfizer. KK has received honoraria Chugai Pharmaceutical, Eli Lilly, and Bristol-Myers Squibb. MS has received grants and contracts from any entity from Taiho Pharmaceutical, Chugai Pharmaceutical, Eli Lilly, Nippon Boehringer Ingelheim, Nippon Kayaku, and Kyowa Hakko Kirin; honoraria from AstraZeneca, MSD K.K, Chugai Pharmaceutical, Taiho Pharmaceutical, Eli Lilly, Ono Pharmaceutical, Bristol-Myers Squibb, Nippon Boehringer Ingelheim, Pfizer, Novartis, Takeda Pharmaceutical, Kyowa Hakko Kirin, Nippon Kayaku, Daiichi-Sankyo Company, Merck Biopharma, and Amgen. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Terashima, Matsumoto, Ozaki, Nakagawa, Nakagome, Terasaki, Iida, Mitsugi, Kuramochi, Okada, Inoue, Matsuki, Kitagawa, Fukuizumi, Onda, Takeuchi, Miyanaga, Kasahara and Seike.)

Background: Autologous stem cell transplantation (ASCT) is a pivotal treatment for lymphoma patients. The BeEAM regimen (Bendamustine, Etoposide, Cytarabine, Melphalan) traditionally relies on cryopreservation, whereas the CEM regimen (Carboplatin, Etoposide, Melphalan) has been optimized for short-duration administration without the need for cryopreservation. This study rigorously compares the clinical and safety profiles of the BeEAM and CEM regimens., Methods: A controlled, randomized clinical trial was conducted with 58 lymphoma patients undergoing ASCT at the International Medical Center (IMC) in Cairo, Egypt. Patients were randomly assigned to either the BeEAM (n = 29) or CEM (n = 29) regimen, with an 18-month follow-up period. Clinical and safety outcomes were meticulously compared, focusing on time to engraftment for neutrophils and platelets, side effects, length of hospitalization, transplant-related mortality (TRM), and survival rates., Results: The findings demonstrate a significant advantage for the CEM regimen. Neutrophil recovery was markedly faster in the CEM group, averaging 8.5 days compared to 14.5 days in the BeEAM group (p < 0.0001). Platelet recovery was similarly expedited, with 11 days in the CEM group versus 23 days in the BeEAM group (p < 0.0001). Hospitalization duration was substantially shorter for CEM patients, averaging 18.5 days compared to 30 days for those on BeEAM (p < 0.0001). Furthermore, overall survival (OS) was significantly higher in the CEM group at 96.55% (95% CI: 84.91-99.44%) compared to 79.31% (95% CI: 63.11-89.75%) in the BeEAM group (p = 0.049). Progression-free survival (PFS) was also notably superior in the CEM group, at 86.21% (95% CI: 86.14-86.28%) versus 62.07% (95% CI: 61.94-62.20%) in the BeEAM group (p = 0.036)., Conclusion: The CEM regimen might demonstrate superiority over the BeEAM regimen, with faster neutrophil and platelet recovery, reduced hospitalization time, and significantly improved overall and progression-free survival rates. Future studies with longer duration and larger sample sizes are warranted., Trial Registration: This study is registered on ClinicalTrials.gov under the registration number NCT05813132 ( https://clinicaltrials.gov/ct2/show/NCT05813132 ). (The first submitted registration date: is March 16, 2023)., (© 2024. The Author(s).)

Purpose: We evaluated the efficacy and safety of antiemetic therapy with olanzapine, a neurokinin-1 receptor antagonist (RA), a 5-hydroxytryptamine-3 (5-HT 3 ) RA, and dexamethasone for preventing chemotherapy-induced nausea and vomiting in patients receiving carboplatin-containing chemotherapy., Patients and Methods: Chemotherapy-naïve patients scheduled to receive carboplatin (AUC ≥5) were randomly assigned to receive either olanzapine 5 mg once daily (olanzapine group) or placebo (placebo group) in combination with aprepitant, a 5-HT 3 RA, and dexamethasone. The primary end point was the complete response (CR; no vomiting and no rescue therapy) rate in the overall phase (0-120 hours). Secondary end points included the proportion of patients free of nausea and safety., Results: In total, 355 patients (78.6% male, median age 72 years, 100% thoracic cancer), including 175 and 180 patients in the olanzapine and placebo groups, respectively, were evaluated. The overall CR rate was 86.9% in the olanzapine group versus 80.6% in the placebo group. The intergroup difference in the overall CR rate was 6.3% (95% CI, -1.3 to 13.9). The proportions of patients free of chemotherapy-induced nausea in the overall (88.6% in the olanzapine group v 75.0% in the placebo group) and delayed (89.7% v 75.6%, respectively) phases were significantly higher in the olanzapine group than in the placebo group (both P < .001). Somnolence was observed in 43 (24.6%) and 41 (22.9%) patients in the olanzapine and placebo groups, respectively, and no events were grade ≥3 in severity., Conclusion: The addition of olanzapine was not associated with a significant increase in the overall CR rate. Regarding the prevention of nausea, adding olanzapine provided better control in patients receiving carboplatin-containing chemotherapy, which needs further exploration.

Objectives: We aimed to evaluate the efficacy and safety of granulocyte-colony stimulating factor (G-CSF) prophylaxis during chemoimmunotherapy with carboplatin plus etoposide and atezolizumab in extensive-stage small cell lung cancer (ES-SCLC)., Methods: This retrospective, multicenter study enrolled ES-SCLC patients receiving carboplatin plus etoposide and atezolizumab, categorized into G-CSF and non-G-CSF groups. Demographic and disease-related data were collected. Response rates, progression-free survival (PFS), overall survival (OS), and toxicity were analyzed., Results: Of 119 patients (median age: 63 years), the overall response rate (ORR) and disease control rate (DCR) were 72.3% and 81.5%, respectively. In the G-CSF group, the ORR was 76.4% compared to 60.0% in the non-G-CSF group ( p  = 0.33), and the DCR was 85.4% versus 70.0%, respectively ( p  = 0.46). Median PFS was 8.3 months (95% CI, 6.8-9.8) in the G-CSF group and 6.8 months (95% CI, 6.2-7.5) in the non-G-CSF group ( p  = 0.24). Median OS was 13.8 months (95% CI, 9.6-18.1) for the G-CSF group and 10.6 months (95% CI, 7.9-13.3) for the non-G-CSF group ( p  = 0.47). Grade 3 ≥ adverse events were similar between groups (49.4% vs. 33.3%, respectively, p  = 0.12)., Conclusion: G-CSF prophylaxis can be safely used in ES-SCLC patients undergoing carboplatin plus etoposide and atezolizumab regimen without significantly altering efficacy or increasing toxicity.

A 71-year-old man with advanced lung adenocarcinoma was treated with carboplatin, pemetrexed, and pembrolizumab in June 2020. Pemetrexed and pembrolizumab maintenance therapy were continued until November 2022. A fever and severe fatigue occurred in December 2022; however, the cause of the infection was inconclusive based on the patient's symptoms, imaging findings, and culture tests. Although the patient was administered antibiotics, his general condition worsened. Considering the possible diagnosis of immune-related cytokine release syndrome (CRS), the patient was administered prednisolone (1 mg/kg/day) and showed improvement. In conclusion, CRS can occur even long after the initial administration of immune checkpoint inhibitor therapy.

Purpose: Tri-weekly carboplatin is an established neoadjuvant treatment for triple-negative breast cancer, enhancing pathological complete response (pCR) and overall survival. This study explores if weekly carboplatin provides lower toxicity and comparable pCR rates., Methods/patients: A retrospective multicenter study (January 2021 to March 2023) compares outcomes of weekly and tri-weekly carboplatin., Results: Among 104 participants, 60% received weekly and 40% tri-weekly treatments. Weekly administration had fewer discontinuations (56.5 vs. 70.7%, p = 0.154). Both schedules exhibited similar overall toxicity (p = 0.087), with slightly higher grade 3-4 toxicity in the tri-weekly group (56.1 vs. 48.4%, p = 0.126). Hematological toxicity was comparable, but the weekly group experienced more diarrhea (p = 0.432) and asthenia (p = 0.012). Weekly treatment correlated with more frequent breast-conserving surgeries (p = 0.004). pCR rates were 50% with weekly and 61% with tri-weekly regimens (p = 0.186)., Conclusions: Weekly carboplatin exhibited comparable toxicity, a trend toward fewer interruptions, and similar pCR rates. Prospective studies are essential for validating these findings., (© 2024. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Purpose: To study the effects of prior pelvic radiotherapy on bone marrow suppression in recurrent cervical cancer patients during chemotherapy. Methods and materials: The cases of 129 patients with recurrent cervical cancer were reviewed, of which 77 patients had pelvic radiotherapy history and another 52 patients with no pelvic radiotherapy history were used as control group. All patients received a chemotherapy regimen of paclitaxel combined with carboplatin (TC) per 21 days for 5-6 times. Hematologic toxicity, including count of red blood cell, white blood cell and neutrophil cell and platelet, was defined by using Common Terminology Criteria for Adverse Events (version 4.0). The relationship between age, body mass index, disease free survival, pathological types, FIGO stages, radiotherapy methods and the degree of bone marrow suppression during chemotherapy was statistically analyzed, respectively, for all recurrent cervical cancer patients. Results: Among 77 patients with previous radiotherapy history, 73 recurrent patients (94.8%) had bone marrow suppression followed by chemotherapy. Recurrent cervical cancer patients without prior radiotherapy (n=52) showed a lower risk of bone marrow suppression followed by chemotherapy (n=39, 75.0%, P < 0.05). The probability of severe bone marrow suppression (grade III-IV) after chemotherapy in recurrent cervical patients with or without history of radiotherapy was 41.6% and 13.5%, respectively (P < 0.05). In univariate analysis, radiotherapy methods were associated with the incidence of grade III-IV bone marrow suppression in recurrent cervical cancer patients (P=0.005). In multivariate analysis, radiotherapy methods and extended-field radiotherapy were the risk factor of grade III-IV bone marrow suppression (χ 2 =16.975, P=0.001). No significant differences in the counts of white blood cell, hemoglobin and platelet were observed before chemotherapy at relapse between patients with and without prior radiotherapy. Reduction of white blood cell counts, absolute value of neutrophil cell and platelet counts composited majority type of grade III and IV bone marrow suppression. Conclusions: The prior pelvic radiotherapy significantly increased the incidence of bone marrow suppression during chemotherapy in recurrent cervical cancer patients. When treating recurrent cervical cancer patients with chemotherapy who had prior radiotherapy, especially for those experienced external beam radiation therapy, essential attention and timely intervention are recommended to ensure completion of chemotherapy and clinical efficacy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: As a substantial waiting time is usually required for radical surgery, safe and effective preoperative neoadjuvant chemotherapy (NAC) is desired for the treatment of locally advanced head and neck squamous cell carcinoma (HNSCC). However, the significance of NAC in advanced HNSCC is still unclear. This study aimed to assess the safety and efficacy of NAC using the paclitaxel, carboplatin, and cetuximab (PCE) regimen., Methods: We retrospectively evaluated the background characteristics, incidence of adverse events, overall response rate (ORR), pathological response, recurrence-free survival (RFS), and overall survival (OS) in 26 patients. Patients receiving the PCE regimen were further divided into two groups based on the number of chemotherapy cycles (one cycle or more) and eligibility for cisplatin. Patients aged ≥ 75 years and those with an estimated glomerular filtration rate (eGFR) < 60 mL/min were classified as ineligible for cisplatin., Results: The median age was 70 (27-81) years. The median eGFR at treatment initiation was 63.2 (41.1-89.7) mL/min. Fourteen (53.8%) patients were ineligible for cisplatin. Grade 3 or higher neutropenia was observed in 11 of 25 (42.3%) patients. No delay in or withdrawal from surgery was observed. The ORR was 65.4%. The 2-year RFS and OS were 61.5% and 76.7%, respectively. No significant differences in safety and efficacy between the number of chemotherapy cycles and cisplatin eligibility were observed., Conclusion: NAC using the PCE regimen for patients with locally advanced HNSCC, including cisplatin-ineligible patients, has acceptable toxicity and favorable efficacy., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Objective: To determine the clinical significance of performing repeated postchemotherapy CBC for cancer-bearing dogs receiving ≥ 4 carboplatin treatments. The secondary aim was to identify risk factors associated with cumulative carboplatin-induced neutropenia in those dogs., Animals: 40 client-owned dogs diagnosed with cancer., Methods: A retrospective study using medical records from a single academic institution during 2012 to 2023. Dogs that received ≥ 4 doses of carboplatin with pre- and postchemotherapy CBCs available were included. Signalment and possible risk factors were recorded. Veterinary Cooperative Oncology Group-Common Terminology Criteria for Adverse Events was used for neutropenia grading., Results: 40 dogs met the inclusion criteria, with a total of 206 prechemotherapy and 188 postchemotherapy CBC results available. The median carboplatin dosage was 300 mg/m2 (range, 200 to 300 mg/m2). The median interval between carboplatin administration and the postchemotherapy CBC was 10 days (range, 6 to 38 days). Eleven dogs developed a grade 2 or higher neutropenia, with 5 dogs developing multiple neutropenic events, for a total of 18 separate events (18/394). Only 2 of 18 neutropenic events were recorded at the 10- to 14-day postchemotherapy CBC. The yield of detecting neutropenia at a postchemotherapy CBC at any carboplatin chemotherapy after the second dose was < 1% (1/149). Dogs that developed neutropenia at the pre-2nd chemotherapy CBC had a significantly higher risk of developing another neutropenic event at subsequent prechemotherapy CBC (P < .001)., Clinical Relevance: The incidence of cumulative neutropenia after 4 to 6 doses of carboplatin is low in cancer-bearing dogs. If a grade 2 or higher neutropenia is observed at or before the second prechemotherapy CBC, the dog is at a higher risk of developing neutropenia following future treatments.

Purpose: Chemotherapy can potentially enhance the activity of immune checkpoint inhibitors by promoting immune priming. The phase Ib/II JAVELIN Chemotherapy Medley trial (NCT03317496) evaluated first-line avelumab + concurrent chemotherapy in patients with advanced urothelial carcinoma or non-small cell lung cancer (NSCLC)., Materials and Methods: Avelumab 800 or 1,200 mg was administered continuously every 3 weeks with standard doses of cisplatin + gemcitabine in patients with urothelial carcinoma, or carboplatin + pemetrexed in patients with nonsquamous NSCLC. Dual primary endpoints were dose-limiting toxicity (DLT; phase Ib) and confirmed objective response (phase Ib/II)., Results: In phase Ib, urothelial carcinoma and NSCLC cohorts received avelumab 800 mg (n = 13 and n = 6, respectively) or 1,200 mg (n = 6 each) + chemotherapy. In evaluable patients with urothelial carcinoma treated with avelumab 800 or 1,200 mg + chemotherapy, DLT occurred in 1/12 (8.3%) and 1/6 (16.7%), respectively; no DLT occurred in the NSCLC cohort. In phase II, 35 additional patients with urothelial carcinoma received avelumab 1,200 mg + chemotherapy. Across all treated patients, safety profiles were similar irrespective of avelumab dose. Objective response rates (95% confidence internal) with avelumab 800 or 1,200 mg + chemotherapy, respectively, across phase Ib/II, were 53.8% (25.1-80.8) and 39.0% (24.2-55.5) in urothelial carcinoma, and 50.0% (11.8-88.2) and 33.3% (4.3-77.7) in NSCLC., Conclusions: Preliminary efficacy and safety findings with avelumab + chemotherapy in urothelial carcinoma and NSCLC were consistent with previous studies of similar combination regimens. Conclusions about clinical activity are limited by small patient numbers., Significance: This phase Ib/II trial evaluated avelumab (immune checkpoint inhibitor) administered concurrently with standard first-line chemotherapy in patients with advanced urothelial carcinoma or advanced nonsquamous NSCLC without actionable mutations. Efficacy and safety appeared consistent with previous studies of similar combinations, although patient numbers were small., (© 2024 The Authors; Published by the American Association for Cancer Research.)

Purpose: This study aimed to assess the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus platinum versus paclitaxel plus platinum as first-line therapy in patients with metastatic or recurrent cervical cancer., Methods: Between October 2020 and March 2022, consecutive patients with diagnosed with metastatic or recurrent cervical cancer were retrospectively recruited in our hospital. Fifty-four patients were treated with nab-paclitaxel plus cisplatin or carboplatin. Twenty-four patients were treated with paclitaxel plus cisplatin or carboplatin. A propensity score matching (PSM) analysis was done using a multivariable logistic regression model. The two groups were compared for objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) in the raw and matched dataset., Results: The nab-paclitaxel group showed a higher ORR than the paclitaxel group both in the raw dataset (72.2% vs. 45.8%; P = 0.025) and matched dataset (81.1% vs. 47.6%; P = 0.008). The median PFS was significantly longer in the nab-paclitaxel group than in the paclitaxel group both in the raw and matched dataset (12 vs. 7 months; P < 0.05). The median OS was not reached in the nab-paclitaxel group compared with 15 months in the paclitaxel group, with a trend toward prolongation. The most common toxicity was hematological adverse events, including grade 3-4 neutropenia, grade 3 anemia and thrombocytopenia in both groups and no statistical differences were observed between the groups (all P > 0.05)., Conclusion: Compared with paclitaxel plus platinum, nab-paclitaxel plus platinum may be an effective and tolerable option as first-line therapy for patients with metastatic or recurrent cervical cancer., (© 2024. The Author(s).)

Background: Platinum-based combination chemotherapy, including cisplatin and carboplatin, are important cytotoxic anti-cancer agents that are widely used to treat various solid tumors. Carboplatin has a similar effect on survival in small cell lung cancer, but generally has a milder toxicity profile when compared with cisplatin. Both may cause moderate or severe neurotoxicity, but ocular neurotoxicity from carboplatin is rarely reported. Case presentation: A 79-year-old man underwent intravenous polychemotherapy (atezolizumab, etoposide, and carboplatin) for small cell lung cancer. One week after the second cycle of chemotherapy, he reported bilateral visual loss as hand motion in both eyes. Dilated fundus examination showed retinal arterial narrowing without hemorrhage, and diffuse choroidal and retinal thinning was observed in an optical coherence tomography scan. Fluorescein angiography revealed significantly delayed circulation without evidence of obstructive lesions. 30-Flicker electroretinogram testing showed a complete absence of cone response in both eyes. The patient's visual acuity aggravated to no light perception in both eyes, even after the cessation of chemotherapy. Conclusions: Carboplatin combination chemotherapy administered at therapeutic doses can result in irreversible visual loss, a side effect that is not widely acknowledged. When using carboplatin, physicians should be aware of its potential ocular toxicity.

Background/aim: There have been advances in the development of immune checkpoint inhibitors for monotherapy and combination therapy with other anticancer agents in recent years. The combination of bevacizumab, carboplatin, and paclitaxel with atezolizumab, an anti-programmed death ligand 1 antibody (ABCP therapy), has been reported to be effective for treating non-small cell lung cancer. However, reports on its adverse events are limited. In this study, a survey and disproportionality analysis based on the Japanese Adverse Drug Event Report (JADER) database was conducted to elucidate the adverse event profile of ABCP therapy., Materials and Methods: The reporting odds ratio (ROR) and information component were used as indicators for the disproportionality analysis. The ROR was also used to assess the changes in the reporting intensity with combination therapy, and the mutual exclusivity of the 95% confidence interval between the compared groups was considered., Results: The reported adverse events of ABCP therapy mirrored those of the individual drugs that constituted it. ABCP therapy enhanced the reporting intensity of adverse events related to leukocytes and the skin, while decreased those related to interstitial lung disease and hepatic function abnormality as immune-related adverse events caused by atezolizumab, and gastrointestinal perforation caused by bevacizumab., Conclusion: Our analysis of data from the JADER database has revealed the adverse event profile of ABCP therapy. Our findings emphasize the importance of effectively managing febrile neutropenia and skin-related adverse events in ABCP therapy., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: Platinum-based chemotherapy is the mainstay of first-line therapy for advanced-stage non-small cell lung cancer (NSCLC). Although carboplatin-induced hypersensitivity reactions (HSRs) commonly occur following multiple cycles of therapy, they are rarely observed during the first cycle of the treatment., Case Report: Here, we report the case of a 70-year-old man with advanced-stage NSCLC who developed HSR possibly caused by carboplatin during the first cycle of induction with platinum-doublet chemotherapy plus pembrolizumab. The patient presented with bronchial obstruction due to a centrally located tumor. No driver mutations were detected, and the programmed death-ligand 1 expression ranged from 1% to 24%. Consequently, the patient was treated with pembrolizumab combined with carboplatin and paclitaxel. However, immediately after the start of carboplatin, the blood pressure and oxygen levels of the patient dropped and he began exhibiting an altered level of consciousness. These findings indicated carboplatin-induced anaphylaxis. Hypotension and oxygen desaturation improved following carboplatin discontinuation and normal saline administration., Management and Outcome: The basophil activation test for both carboplatin and cisplatin was negative. Thus, the risk of anaphylaxis owing to both drugs was ruled out, and carboplatin was believed to have induced grade 3 HSR. Subsequently, carboplatin-based chemotherapy was switched to cisplatin-based chemotherapy. HSR was not observed during the four treatment cycles with pembrolizumab, cisplatin, and pemetrexed, and best response was partial response., Discussion: Cisplatin-based chemotherapy could be used as an alternate treatment in patients with NSCLC who develop severe carboplatin-induced HSR., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: A standard treatment for fit, older patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) is yet to be established. In the previous EXTREME trial, few older patients were included. We aimed to evaluate the efficacy and tolerance of an adapted EXTREME regimen in fit, older patients with recurrent or metastatic HNSCC., Methods: This single-arm, phase 2 study was done at 22 centres in France. Eligible patients were aged 70 years or older and assessed as not frail (fit) using the ELAN Geriatric Evaluation (EGE) and had recurrent or metastatic HNSCC in the first-line setting that was not eligible for local therapy (surgery or radiotherapy), and an Eastern Cooperative Oncology Group performance status of 0-1. The adapted EXTREME regimen consisted of six cycles of fluorouracil 4000 mg/m 2 on days 1-4, carboplatin with an area under the curve of 5 on day 1, and cetuximab on days 1, 8, and 15 (400 mg/m 2 on cycle 1-day 1, and 250 mg/m 2 subsequently), all intravenously, with cycles starting every 21 days. In patients with disease control after two to six cycles, cetuximab 500 mg/m 2 was continued once every 2 weeks as maintenance therapy until disease progression or unacceptable toxicity. Granulocyte colony-stimulating factor was systematically administered and erythropoietin was recommended during chemotherapy. The study was based on the two-stage Bryant and Day design, combining efficacy and toxicity endpoints. The primary efficacy endpoint was objective response rate at week 12 after the start of treatment, assessed by central review (with an unacceptable rate of ≤15%). The primary toxicity endpoint was morbidity, defined as grade 4-5 adverse events, or cutaneous rash (grade ≥3) that required cetuximab to be discontinued, during the chemotherapy phase, or a decrease in functional autonomy (Activities of Daily Living score decrease ≥2 points from baseline) at 1 month after the end of chemotherapy (with an unacceptable morbidity rate of >40%). Analysis of the coprimary endpoints, and of safety in the chemotherapy phase, was based on the per-protocol population, defined as eligible patients who received at least one cycle of the adapted EXTREME regimen. Safety in the maintenance phase was assessed in all patients who received at least one dose of cetuximab as maintenance therapy. The study is registered with ClinicalTrials.gov, NCT01864772, and is completed., Findings: Between Sept 27, 2013, and June 20, 2018, 85 patients were enrolled, of whom 78 were in the per-protocol population. 66 (85%) patients were male and 12 (15%) were female, and the median age was 75 years (IQR 72-79). The median number of chemotherapy cycles received was five (IQR 3-6). Objective response at week 12 was observed in 31 patients (40% [95% CI 30-51]) and morbidity events were observed in 24 patients (31% [22-42]). No fatal adverse events occurred. Four patients presented with a decrease in functional autonomy 1 month after the end of chemotherapy versus baseline. During chemotherapy, the most common grade 3-4 adverse events were haematological events (leukopenia [22 patients; 28%], neutropenia [20; 26%], thrombocytopenia [15; 19%], and anaemia [12; 15%]), oral mucositis (14; 18%), fatigue (11; 14%), rash acneiform (ten; 13%), and hypomagnesaemia (nine; 12%). Among 44 patients who received cetuximab during the maintenance phase, the most common grade 3-4 adverse events were hypomagnesaemia (six patients; 14%) and acneiform rash (six; 14%)., Interpretation: The study met its primary objectives on objective response and morbidity, and showed overall survival to be as good as in younger patients treated with standard regimens, indicating that the adapted EXTREME regimen could be used in older patients with recurrent or metastatic HNSCC who are deemed fit with use of a geriatric evaluation tool adapted to patients with head and neck cancer, such as the EGE., Funding: French programme PAIR-VADS 2011 (sponsored by the National Cancer Institute, the Fondation ARC, and the Ligue Contre le Cancer), Sandoz, GEFLUC, and GEMLUC., Translation: For the French translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests JG has been an advisory board member for BMS, Hookipa, MSD, Merck, Nanobiotix, and Roche, outside the submitted work; reports personal fees from MSD, outside the submitted work; and has received grant support during the study, paid to his institution, from the GEMLUC and GEFLUC, and the French National Cancer Institute, the Fondation ARC, and the Ligue Contre le Cancer, through the French programme PAIR-VADS 2011. F-RF reports travel support for congress from Merck Serono, outside the submitted work. ES-B reports personal fees from MSD and Merck Serono, and support for attending meetings or travel, or both, from MSD and Merck Serono, outside the submitted work. JF reports personal fees and non-financial support from MSD and Merck, and personal fees from AstraZeneca, BMS, Roche, Rakuten, Elevar, Hookipa, Sanofi, and Seagen, during the conduct of the study; and has been an advisory board member for Roche, Seagen, and Elevar, outside the submitted work. FR reports personal fees and non-financial support from Merck, outside the submitted work. CF reports personal fees from Astellas Pharma, AstraZeneca, Biogaran, BMS, Chugai Pharma France, Clovis Oncology, Eisai, GSK, Leo Pharma, Lilly, MSD Oncology, Novartis, Pfizer, Pierre Fabre, Seagen, and Viatris, and non-financial support from AstraZeneca, Janssen Oncology, Leo Pharma, and Pierre Fabre, outside the submitted work. TC reports personal fees from Merck and has been an advisory board member for MSD outside the submitted work. PDa reports personal fees from Lilly and has been advisory board member for Pfizer and MSD, outside the submitted work. SL has participated on advisory boards of Merck and BMS, outside the submitted work. AA reports grants from the French programme PAIR-VADS 2011 funded by the French National Cancer Institute, the Fondation ARC, and the Ligue Contre le Cancer, and grants from Sandoz, during the conduct of the study, and other from MSD, outside the submitted work; all paid to her institution. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Esophageal cancer (EC) is a major cause of cancer-related deaths worldwide, bringing tremendous pressure to the healthcare system and patients. Esophageal squamous cell carcinoma (ESCC) is the main subtype of EC in the Chinese population., Objectives: This study aimed to extend the neoadjuvant therapy cycle to 4 cycles and evaluate the efficacy and safety of neoadjuvant camrelizumab combined with chemotherapy for the treatment of resectable ESCC., Material and Methods: The enrolled patients received neoadjuvant camrelizumab (200 mg, day 1), nab-paclitaxel (260 mg/m2, day 1) and carboplatin (area under curve; 5 mg/mL/min) every 21 days for 4 cycles, and surgery was performed within 4-6 weeks after the first day of the 4th treatment cycle. The primary endpoint of the study was the pathological complete response (pCR) rate., Results: From December 15, 2021, to October 1, 2022, a total of 35 patients were enrolled in the study. All patients completed the full 4-cycle treatment and were deemed fit for surgical intervention. Thirty-four (97.1%) patients achieved R0 resection, 18 (51.4%) showed a pCR rate, and 27 (77.1%) achieved a major pathological response (MPR). Tumor degradation was observed in 30 out of 35 patients (85.7%). Multivariate logistic regression analyses further confirmed that age (odds ratio (OR) = 6.710, 95% confidence interval (95% CI): 3.512-44.403) and programmed death-ligand 1 (PD-L1) (OR = 2.855, 95% CI: 1.181-3.079) were independent predictors of pCR. The most prevalent adverse event (AE) was leukopenia, which was experienced by 23 out of 35 patients (65.7%). Grade 3 or higher AEs included leukopenia in 2 cases (5.7%) and neutropenia in 12 cases (34.3%). No delays in surgery were observed., Conclusions: As demonstrated in this study, the 4 cycles of camrelizumab combined with nab-paclitaxel and carboplatin, which exhibited a relatively high pCR rate and acceptable safety, suggest a strong rationale for its further evaluation in resectable ESCC.

Purpose: Previous studies have reported the benefit of dual HER2-targeting combined to neoadjuvant chemotherapy in HER2-amplified breast cancer (HER2 + BC). Moreover, besides the cardiac toxicity following their association to Trastuzumab, anthracyclines chemotherapy may not profit all patients. The NeoTOP study was designed to evaluate the complementary action of Trastuzumab and Pertuzumab, and the relevance of an anthracycline-based regimen according to TOP2A amplification status., Methods: Open-label, multicentre, phase II study. Eligible patients were aged ≥ 18 with untreated, operable, histologically confirmed HER2 + BC. After centralized review of TOP2A status, TOP2A-amplified (TOP2A+) patients received FEC100 for 3 cycles then 3 cycles of Trastuzumab (8 mg/kg then 6 mg/kg), Pertuzumab (840 mg/kg then 420 mg/kg), and Docetaxel (75mg/m 2 then 100mg/m 2 ). TOP2A-not amplified (TOP2A-) patients received 6 cycles of Docetaxel (75mg/m 2 ) and Carboplatin (target AUC 6 mg/ml/min) plus Trastuzumab and Pertuzumab. Primary endpoint was pathological Complete Response (pCR) using Chevallier's classification. Secondary endpoints included pCR (Sataloff), Progression-Free Survival (PFS), Overall Survival (OS), and toxicity., Results: Out of 74 patients, 41 and 33 were allocated to the TOP2A + and TOP2A- groups respectively. pCR rates (Chevallier) were 74.4% (95%CI: 58.9-85.4) vs. 71.9% (95%CI: 54.6-84.4) in the TOP2A + vs. TOP2A- groups. pCR rates (Sataloff), 5-year PFS and OS were 70.6% (95%CI: 53.8-83.2) vs. 61.5% (95%CI: 42.5-77.6), 82.4% (95%CI: 62.2-93.6) vs. 100% (95%CI: 74.1-100), and 90% (95%CI: 69.8-98.3) vs. 100% (95%CI: 74.1-100). Toxicity profile was consistent with previous reports., Conclusion: Our results showed high pCR rates with Trastuzumab and Pertuzumab associated to chemotherapy. They were similar in TOP2A + and TOP2A- groups and the current role of neoadjuvant anthracycline-based chemotherapy remains questioned., Trial Registration Number: NCT02339532 (registered on 14/12/14)., (© 2024. The Author(s).)

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer associated with shorter survival and a higher likelihood of recurrence. In early TNBC, platinum chemotherapy has been shown to improve pathological complete response (pCR); however, its effect on long-term survival outcomes has not been fully elucidated., Methods: Randomised controlled trials examining neoadjuvant or adjuvant platinum chemotherapy for early TNBC were included. Primary outcomes were disease-free survival (DFS) and overall survival (OS). Secondary outcomes were pCR, treatment adherence, grade III or IV toxicity related to chemotherapy, and quality of life., Results: From 3972 records, we included 20 published studies. All studies reporting DFS and OS used carboplatin. Inclusion of platinum chemotherapy improved DFS (neoadjuvant: hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.53 to 0.75; adjuvant: HR 0.69, 95% CI 0.54 to 0.88) and OS (neoadjuvant: HR 0.69, 95% CI 0.55 to 0.86; adjuvant: 0.70, 95% CI 0.50 to 0.96). Our analysis confirmed platinum chemotherapy increased pCR rates (risk ratio (RR) 1.44, 95% CI 1.31 to 1.59). There were no differences seen in examined subgroups. Platinum chemotherapy was associated with reduced dose intensity and increased haematological toxicity., Conclusions: Platinum-based chemotherapy using carboplatin in the adjuvant or neoadjuvant setting improves long-term outcomes of DFS and OS in early TNBC, with no evidence of differences by subgroup. This was at the cost of more frequent chemotherapy delays and dose reductions, and greater haematological toxicity. These findings support the use of platinum-based chemotherapy for people with early TNBC., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Pembrolizumab plus epacadostat (indoleamine 2,3-dioxygenase-1 inhibitor) was well tolerated in Japanese patients with advanced solid tumors in part A of the nonrandomized, open-label, phase 1 KEYNOTE-434 study (NCT02862457). We report results from part B, which evaluated epacadostat plus pembrolizumab and chemotherapy in Japanese patients with advanced non-small-cell lung cancer (NSCLC)., Methods: Eligible patients aged ≥ 20 years had histologically or cytologically confirmed stage IIIB or IV NSCLC with no prior systemic therapy, and ECOG performance status of 0 or 1. Patients received epacadostat 100 mg orally twice-daily, pembrolizumab 200 mg intravenously every-3-weeks for ≤ 35 cycles, and 4 cycles of chemotherapy (cohort 1: cisplatin plus pemetrexed, non-squamous; cohort 2: carboplatin plus pemetrexed, non-squamous; cohort 3: carboplatin plus paclitaxel, squamous or non-squamous). Primary endpoint was incidence of dose-limiting toxicities (DLTs). Following unfavorable results from other studies, a protocol amendment removed epacadostat from the treatment combination., Results: Of 19 patients, 7 were enrolled in cohort 1, and 6 each in cohorts 2 and 3. Median follow-up was 13.7 (range, 4.2-27.8) months. Five of 17 (29%) DLT-evaluable patients experienced ≥ 1 DLT (cohort 1, n = 1; cohorts 2 and 3, n = 2 each); most commonly maculopapular rash (grade 3, n = 3) and increased alanine aminotransferase (grade 2, n = 1; grade 3, n = 2). All patients experienced treatment-related adverse events (AEs); 58% experienced grade 3 or 4 treatment-related AEs. Objective response rate was 47%., Conclusion: The combination of epacadostat plus pembrolizumab and chemotherapy was found to be tolerable in Japanese patients with advanced NSCLC., Trial Registration: ClinicalTrials.gov , NCT02862457., (© 2023. Merck & Co., Inc., Rahway, NJ, USA and its affiliates.)