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Inotuzumab ozogamicin (InO), a CD22-directed antibody conjugated to calicheamicin, has demonstrated excellent efficacy in B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). It has been used for patients with relapsed or refractory BCP-ALL as a bridge to allo-HCT. Children with Down syndrome (DS) have an increased risk of BCP-ALL and higher rates of relapse and toxicity, including treatment-related mortality. Although allo-HCT is potentially curative for relapsed or refractory ALL, post-transplant leukemic relapse rates and transplant-related mortality are dismal in patients with DS-ALL, which results in less frequent use of allo-HCT in this group than in the non-DS population. Therefore, novel and less toxic therapeutic strategies are required to improve outcomes. Here we report the case of a child with DS who was diagnosed with a second relapse of BCP-ALL and has maintained complete remission through regular single-agent InO therapy. Single-agent maintenance using InO can be a good option to avoid subsequent relapse in patients with relapsed or refractory BCP-ALL who cannot proceed to allo-HCT and require less-toxic treatments. New findings: Inotuzumab ozogamicin (InO), an anti-CD22 monoclonal antibody bound to calicheamicin, has significant activity against BCP-ALL and has been used for patients with relapsed or refractory BCP-ALL as a bridge to allogeneic hematopoietic transplantation (allo-HCT). However, allo-HCT is not suitable for patients at high risk of treatment-related toxicity, including those with Down syndrome (DS). We describe a boy with second relapsed DS-associated BCP-ALL maintaining complete remission with regular InO administration. InO-mediated maintenance therapy may be a good option to avoid subsequent relapse in patients with relapsed or refractory BCP-ALL who cannot proceed to allo-HCT and require less-toxic therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Laryngeal cancer is a common head and neck cancer. Surgical treatment can impair patients' voice and swallowing function, making definitive radiotherapy a viable alternative for locally advanced cases. Methods: To compare the outcomes of definitive versus adjuvant radiotherapy in patients with primary locally advanced laryngeal cancer, we retrospectively evaluated consecutive patients treated from 2007 to 2020. We assessed and compared the median and 3-year overall survival (OS), disease-free survival (DFS), distant metastasis control (DMC), and local recurrence-free survival (LRC) in all patients and in T4 patients exclusively. Results: One hundred patients were studied, including definitive (N = 64) and adjuvant (N = 36) radiotherapy. The median follow-up was 29 months. Overall, the median OS in the definitive vs. adjuvant group was 100 months (95%CI = 46.5-153.5) vs. not reached, respectively (log-rank P = 0.506). The median DFS in the definitive vs. adjuvant group was 20 months (95%CI = 7.7–32.3) vs. not reached, respectively (log-rank P = 0.148). Three-year OS and DFS rates in all patients were 64% (95%CI: 48–78) vs. 75% (95%CI: 55–95) and 43% (95%CI:29–57) vs. 61% (95%CI: 41–81) in the definitive vs. adjuvant groups, respectively. Among T4 patients, the median OS in the definitive RT group vs. adjuvant group was not reached vs. 48 (95%CI = 0-105.3), respectively (log-rank P = 0.788). The median DFS in the definitive RT group vs. adjuvant group was 12 months (95%CI = 9.34–14.65) vs. 36 months (95%CI = 4.4–67.5), respectively (log-rank P = 0.868). Three-year OS and DFS rates were 71% (95%CI: 42–100) vs. 75% (95%CI: 50–100) and 40% (95%CI:21–79) vs. 56% (95%CI: 25–87) in the definitive vs. adjuvant groups, respectively. Conclusions: Our analysis suggests that definitive radiotherapy in laryngeal cancer does not lead to a poorer outcome than total laryngectomy followed by adjuvant radiotherapy. In T4 patients, our findings should reassure clinicians and patients about the viability of definitive radiotherapy as a treatment approach. [ABSTRACT FROM AUTHOR]

Abstract Relapse remains a major cause of treatment failure following allogeneic stem cell transplantation (allo‐SCT) for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We retrospectively investigated low‐dose decitabine and venetoclax (DEC/VEN) as post‐transplant maintenance in 26 older patients with AML and MDS. The cumulative incidence of day 100 gIII‐IV acute graft versus host disease (GVHD) and 1‐year moderate‐severe chronic GVHD was 5% and 26%, respectively. One patient relapsed 14 m after transplant. The 1‐year non‐relapse mortality and survival were 11% and 84%, respectively. DEC/VEN is a safe and potentially effective strategy to reduce the risk of post‐transplant relapse.

Background & aimsThe IM-UNITI study and long-term extension (LTE) evaluated the long-term efficacy, safety, and immunogenicity of subcutaneous ustekinumab maintenance therapy in patients with Crohn's disease. Here, we report the final results of IM-UNITI LTE through 5 years.MethodsPatients completing safety and efficacy evaluations at week 44 of the maintenance study were eligible to participate in the LTE and continue the treatment they were receiving. Unblinding occurred after completion of maintenance study analyses (August 2015), and patients receiving placebo were discontinued from the study after unblinding. No dose adjustment occurred in the LTE. Efficacy assessments were conducted every 12 weeks until unblinding and at dosing visits thereafter through week 252. Serum ustekinumab concentrations and antidrug antibodies were evaluated through weeks 252 and 272, respectively.ResultsUsing an intent-to-treat analysis of all patients randomized to ustekinumab at maintenance baseline, 34.4% of patients in the every-8-weeks group and 28.7% in the every-12-weeks group were in clinical remission at week 252. Corresponding remission rates among patients who entered the LTE were 54.9% and 45.2%. Overall, adverse event rates (per 100 patient-years) from maintenance week 0 through the final visit generally were similar in the placebo and combined ustekinumab groups for all adverse events (440.3 vs 327.6), serious adverse events (19.3 vs 17.5), infections (99.8 vs 93.8), and serious infections (3.9 vs 3.4). Serum ustekinumab concentrations were maintained throughout the LTE. Antidrug antibodies occurred in 5.8% of patients who received ustekinumab during induction and maintenance and continued in the LTE.ConclusionsPatients receiving subcutaneous ustekinumab maintained clinical remission through 5 years. No new safety signals were observed. ClinicalTrials.gov number NCT01369355.

ObjectiveIn the Phase 3 VELIA trial (NCT02470585), veliparib added to carboplatin plus paclitaxel concomitantly and as maintenance for women with newly-diagnosed advanced ovarian cancer significantly improved progression-free survival (PFS) versus chemotherapy alone. Here we present exploratory analyses by paclitaxel dosing schedule and germline BRCA (gBRCA) status.MethodsWomen with untreated ovarian carcinoma were randomized (1:1:1) to: veliparib during chemotherapy and maintenance (veliparib-throughout), veliparib during chemotherapy followed by placebo maintenance (veliparib-combination only), or placebo during chemotherapy and maintenance (control). Chemotherapy included carboplatin plus dose-dense (DD; weekly) or every-3-week (Q3W) paclitaxel (a stratification factor at randomization), selected at the investigator's discretion pre-randomization. PFS was assessed by paclitaxel dosing schedule using a Cox proportional hazard model adjusted by treatment arm and stratification factors; safety was analyzed based on paclitaxel dosing schedule and gBRCA status.Results1132 patients were analyzed by paclitaxel schedule. Pooled treatment arms demonstrated longer median PFS with DD (n = 586) versus Q3W (n = 546) paclitaxel (ITT: 20.5 vs 15.7 months, hazard ratio [HR] 0.77; homologous recombination proficient cancer: 15.1 vs 11.8 months, HR 0.64; BRCAwt: 18.0 vs 12.9 months, HR 0.70). Comparison between arms favored veliparib-throughout versus control in both DD (PFS, 24.2 vs 18.3 months, hazard ratio 0.67) and Q3W (19.3 vs 14.6, hazard ratio 0.69) subgroups. DD paclitaxel was associated with higher incidence of Grade 3/4 neutropenia, fatigue, and anemia versus Q3W. There were no differences in toxicity between gBRCAm (n = 211) and gBRCAwt (n = 902) subgroups.ConclusionsDD paclitaxel was tolerable and associated with longer PFS in the HR proficient and gBRCAwt groups, versus Q3W. gBRCA status did not impact safety.

PurposeThe role of maintenance therapy for gastric (GC) or gastroesophageal junction cancer (GEJC) is unclear. We investigated avelumab (anti-programmed death ligand-1 [PD-L1]) maintenance after first-line induction chemotherapy for GC/GEJC.Patients and methodsJAVELIN Gastric 100 was a global, open-label, phase III trial. Eligible patients had untreated, unresectable, human epidermal growth factor receptor 2-negative, locally advanced or metastatic GC or GEJC. Patients without progressive disease after 12 weeks of first-line chemotherapy with oxaliplatin plus a fluoropyrimidine were randomly assigned 1:1 to avelumab 10 mg/kg every 2 weeks or continued chemotherapy, stratified by region (Asia v non-Asia). The primary end point was overall survival (OS) after induction chemotherapy in all randomly assigned patients or the PD-L1-positive randomly assigned population (≥ 1% of tumor cells; 73-10 assay).ResultsA total of 805 patients received induction; 499 were randomly assigned to avelumab (n = 249) or continued chemotherapy (n = 250). Median OS was 10.4 months (95% CI, 9.1 to 12.0 months) versus 10.9 months (95% CI, 9.6 to 12.4 months) and 24-month OS rate was 22.1% versus 15.5% with avelumab versus chemotherapy, respectively (hazard ratio [HR], 0.91; 95% CI, 0.74 to 1.11; P = .1779). In the PD-L1-positive population (n = 54), the HR for OS was 1.13 (95% CI, 0.57 to 2.23; P = .6352). In an exploratory analysis of the PD-L1-positive population, defined as combined positive score ≥ 1 (22C3 assay; n = 137), median OS was 14.9 months (95% CI, 8.7 to 17.3 months) with avelumab versus 11.6 months (95% CI, 8.4 to 12.6 months) with chemotherapy (unstratified HR, 0.72; 95% CI, 0.49 to 1.05). With avelumab and chemotherapy, treatment-related adverse events (TRAEs) occurred in 149 (61.3%) and 184 (77.3%) patients, including grade ≥ 3 TRAEs in 31 (12.8%) and 78 (32.8%) patients, respectively.ConclusionJAVELIN Gastric 100 did not demonstrate superior OS with avelumab maintenance versus continued chemotherapy in patients with advanced GC or GEJC overall or in a prespecified PD-L1-positive population.

Neuroblastoma is a sympathetic nervous system tumor, primarily presenting in children under 6 years of age. The long-term prognosis for patients with high-risk neuroblastoma (HRNB) remains poor despite aggressive multimodal therapy. This report provides an update to a phase II trial evaluating DFMO as maintenance therapy in HRNB. Event-free survival (EFS) and overall survival (OS) of 81 subjects with HRNB treated with standard COG induction, consolidation and immunotherapy followed by 2 years of DFMO on the NMTRC003/003b Phase II trial were compared to a historical cohort of 76 HRNB patients treated at Beat Childhood Cancer Research Consortium (BCC) hospitals who were disease-free after completion of standard upfront therapy and did not receive DFMO. The 2- and 5-year EFS were 86.4% [95% confidence interval (CI) 79.3%-94.2%] and 85.2% [77.8%-93.3%] for the NMTRC003/003b subset vs 78.3% [69.5%-88.3%] and 65.6% [55.5%-77.5%] for the historical control group. The 2- and 5-year OS were 98.8% [96.4-100%] and 95.1% [90.5%-99.9%] vs 94.4% [89.3%-99.9%] and 81.6% [73.0%-91.2%], respectively. DFMO maintenance for HRNB after completion of standard of care therapy was associated with improved EFS and OS relative to historical controls treated at the same institutions. These results support additional investigations into the potential role of DFMO in preventing relapse in HRNB.

On 13 June 2018, Genentech, Inc. issued a press release announcing that the US FDA had approved the antiangiogenesis drug, bevacizumab, in combination with chemotherapy for frontline and maintenance therapy for women with newly diagnosed ovarian cancer. Regulatory approval was based on the National Cancer Institute-sponsored Gynecologic Oncology Group (GOG) protocol 0218, the Phase III, randomized, placebo-controlled, double-blind, multi-center and multi-national clinical trial that met its primary end point, progression-free survival. Bevacizumab is now approved in the frontline, platinum-sensitive recurrent and platinum-resistant recurrent settings for epithelial ovarian cancer. This review will address the broad range of clinical trials addressing the efficacy of bevacizumab use in ovarian cancer.

Abstract Background and Objective In general, there are not many studies exploring the clinical value of adjuvant chemotherapy or maintenance chemotherapy (AC/MC) after induction chemotherapy and concurrent chemoradiotherapy (IC+CCRT+AC/MC). The purpose of this study was to establish a clinical nomogram for the use of AC/MC in patients with locoregionally advanced nasopharyngeal carcinoma (LA‐NPC). Material and Methods Two centers (Guangzhou Medical University Cancer Center [N = 1226] and Zhongshan People's Hospital [N = 150]) recruited 1376 patients with LA‐NPC. All the patients underwent IC+CCRT; 560 patients received AC with cisplatin/nedaplatin plus docetaxel/paclitaxel (TP) or cisplatin/nedaplatin plus fluorouracil (PF), and 81 patients received MC with S‐1. Multivariate Cox regression was used to confirm optimal predictors of progression‐free survival (PFS), and a nomogram was established to identify patients into low‐risk and high‐risk cohorts. Additionally, bootstrap internal validation was performed to further verify our nomogram. Results After propensity score matching (PSM), the survival curves were not statistically different between IC+CCRT+AC/MC and IC+CCRT (all p > 0.05). Then, a nomogram was developed based on variables that were screened by univariate and multivariate Cox regression, including N stage, cumulative platinum dose during CCRT, body mass index (BMI), IC cycles, IC regimen and cervical lymph node (CLN) necrosis and infiltration of adjacent tissues. The results of the nomogram showed that the high‐risk cohort had greatly worse 5‐year DMFS, LRFS, PFS and OS compared to low‐risk cohort (all p

Limited data exist on the management of patients with locally advanced (aPC) or metastatic pancreatic (mPC) cancer who achieve stable disease/response after first‐line chemotherapy. In this setting, maintenance therapy is important to minimize toxicity while preserving survival benefits. The aim of this study is to conduct a narrative review of the evidence available on the topic and present the results of a retrospective case series of patients with aPC or mPC who received maintenance therapy following a good response to induction chemotherapy. Olaparib is the only drug approved for maintenance therapy in patients with metastatic pancreatic cancer and germline Breast Cancer gene mutation. Data from several trials, including the phase II PANOPTIMOX‐PRODIGE35 trial, showed clinical benefit from the use of 5‐fluorouracil (5‐FU) as maintenance. We also conducted a case series including 12 patients who received FOLFIRINOX as induction chemotherapy for aPC or mPC followed by fluorouracil (5‐FU) or FOLFIRI maintenance therapy. Median progression‐free survival is 22.13 months which is higher than that reported in the literature, which ranges between 5 and 10.6 months. Although further conclusions cannot be drawn because of the small sample size, the results are promising and encourage further exploration of this topic in larger prospective trials. [ABSTRACT FROM AUTHOR]

Simple Summary: The updated results of the RMS2005 randomized study confirm that patients with non-metastatic high risk rhabdomyosarcoma have an improved survival when maintenance chemotherapy (MC) with vinorelbine and low dose cyclophosphamide is added to the standard multidisciplinary treatment. A more recent randomized study adopted the same strategy, but different drugs were used in the MC phase (trofosfamide, idarubicin and etoposide). No survival improvement was evident in the MC group, suggesting that not all types of MC are equally effective. A revision of the literature demonstrates that the role of MC in patients with metastatic or relapsed RMS may be a promising approach but need more investigations. Maintenance chemotherapy (MC) defines the administration of prolonged relatively low-intensity chemotherapy with the aim of "maintaining" tumor complete remission. This paper aims to report an update of the RMS2005 trial, which demonstrated better survival for patients with high-risk localized rhabdomyosarcoma (RMS) when MC with vinorelbine and low-dose cyclophosphamide was added to standard chemotherapy, and to discuss the published experience on MC in RMS. In the RMS2005 study, the outcome for patients receiving MC vs. those who stopped the treatment remains superior, with a 5-year disease-free survival of 78.1% vs. 70.1% (p = 0.056) and overall survival of 85.0% vs. 72.4% (p = 0.008), respectively. We found seven papers describing MC in RMS, but only one randomized trial that did not demonstrate any advantage when MC with eight courses of trofosfamide/idarubicine alternating with trofosfamide/etoposide has been employed in high-risk RMS. The use of MC showed better results in comparison to high-dose chemotherapy in non-randomized studies, including metastatic patients, and demonstrated feasibility and tolerability in relapsed RMS. Many aspects of MC in RMS need to be investigated, including the best drug combination and the optimal duration. The ongoing EpSSG trial will try to answer some of these questions. [ABSTRACT FROM AUTHOR]

Background Long-term corticosteroid therapy is the standard of care for treatment of cardiac sarcoidosis (CS). The efficacy of long-term corticosteroid-sparing immunosuppression in CS is unknown. The goal of this study was to assess the efficacy of methotrexate with or without adalimumab for long-term disease suppression in CS, and to assess recurrence and adverse event rates after immunosuppression discontinuation. Methods and Results Retrospective chart review identified treatment-naive CS patients at a single academic medical center who received corticosteroid-sparing maintenance therapy. Demographics, cardiac uptake of 18-fluorodeoxyglucose, and adverse cardiac events were compared before and during treatment and between those with persistent or interrupted immunosuppression. Twenty-eight CS patients were followed for a mean 4.1 (SD 1.5) years. Twenty-five patients received 4 to 8 weeks of high-dose prednisone (>30 mg/day), followed by taper and maintenance therapy with methotrexate±low-dose prednisone (low-dose prednisone,

Staying current on the rapidly evolving therapeutic landscape in oncology is challenging for clinicians. This commentary discusses exciting practice‐changing data specific to ovarian cancer.

PurposeTo determine the proportion of treatment-experienced eyes with exudative age-related macular degeneration successfully treated with every-4-week aflibercept that can be kept dry on fixed every-8-week aflibercept injections (maintenance).MethodsIn this retrospective chart review, we evaluated our cohort of patients treated with a treatment paradigm for CNV in AMD. Initially, patients were treated with bevacizumab or ranibizumab and switched to every-4-week aflibercept when therapeutic responses were not durable or were suboptimal. Maintenance every-8-week therapy was initiated when the retina was completely dry on every-4-week aflibercept therapy. The primary outcome measure was recurrence of exudation on optical coherence tomography (OCT) during maintenance.ResultsThirty-six eyes of 31 consecutive patients with median age of 79 years (range, 65-89) were included. Maintenance was started after a median of 34 (range, 8-88) injections. Recurrence was observed in 20 eyes (55%). Of these, 11 eyes (31%) reactivated at 8 weeks. Median time to failure of maintenance schedule was 40 weeks by Kaplan-Meier analysis. Baseline demographic and anatomic characteristics were not associated with failure of maintenance schedule.ConclusionIn treatment-experienced eyes that respond completely to every-4-week aflibercept, maintenance therapy with every-8-week injections can only temporarily maintain anatomic success with the majority of eyes developing recurring activity. This regimen fails early in one third of eyes and has a median effective duration of 40 weeks. Aflibercept appears to be inadequate to maintain control of exudation in most eyes in at least half of eyes undergoing long-term therapy.

PurposeSingle-cycle melphalan 200 mg/m2 and autologous hematopoietic cell transplantation (AHCT) followed by lenalidomide (len) maintenance have improved progression-free survival (PFS) and overall survival (OS) for transplantation-eligible patients with multiple myeloma (MM). We designed a prospective, randomized, phase III study to test additional interventions to improve PFS by comparing AHCT, tandem AHCT (AHCT/AHCT), and AHCT and four subsequent cycles of len, bortezomib, and dexamethasone (RVD; AHCT + RVD), all followed by len until disease progression.Patients and methodsPatients with symptomatic MM within 12 months from starting therapy and without progression who were age 70 years or younger were randomly assigned to AHCT/AHCT + len (n = 247), AHCT + RVD + len (n = 254), or AHCT + len (n = 257). The primary end point was 38-month PFS.ResultsThe study population had a median age of 56 years (range, 20 to 70 years); 24% of patients had high-risk MM, 73% had a triple-drug regimen as initial therapy, and 18% were in complete response at enrollment. The 38-month PFS rate was 58.5% (95% CI, 51.7% to 64.6%) for AHCT/AHCT + len, 57.8% (95% CI, 51.4% to 63.7%) for AHCT + RVD + len, and 53.9% (95% CI, 47.4% to 60%) for AHCT + len. For AHCT/AHCT + len, AHCT + RVD + len, and AHCT + len, the OS rates were 81.8% (95% CI, 76.2% to 86.2%), 85.4% (95% CI, 80.4% to 89.3%), and 83.7% (95% CI, 78.4% to 87.8%), respectively, and the complete response rates at 1 year were 50.5% (n = 192), 58.4% (n = 209), and 47.1% (n = 208), respectively. Toxicity profiles and development of second primary malignancies were similar across treatment arms.ConclusionSecond AHCT or RVD consolidation as post-AHCT interventions for the up-front treatment of transplantation-eligible patients with MM did not improve PFS or OS. Single AHCT and len should remain as the standard approach for this population.

Purpose: Oxaliplatin, a component of the capecitabine plus oxaliplatin (XELOX) regimen, has a more favorable toxicity profile than cisplatin in patients with advanced gastric cancer (GC). However, oxaliplatin can induce sensory neuropathy and cumulative, dose-related toxicities. Thus, the capecitabine maintenance regimen may achieve the maximum treatment effect while reducing the cumulative neurotoxicity of oxaliplatin. This study aimed to compare the survival of patients with advanced GC between capecitabine maintenance and observation after 1st line XELOX chemotherapy. Materials and Methods: Sixty-three patients treated with six cycles of XELOX for advanced GC in six hospitals of the Catholic University of Korea were randomized 1:1 to receive capecitabine maintenance or observation. The primary endpoint was progression-free survival (PFS), analyzed using a two-sided log-rank test stratified at a 5% significance level. Results: Between 2015 and 2020, 32 and 31 patients were randomized into the maintenance and observation groups, respectively. After randomization, the median number of capecitabine maintenance cycles was 6. The PFS was significantly higher in the maintenance group than the observation group (6.3 vs. 4.1 months, P=0.010). Overall survival was not significantly different between the 2 groups (18.2 vs. 16.5 months, P=0.624). Toxicities, such as hand-foot syndrome, were reported in some maintenance group patients. Maintenance treatment was a significant factor associated with PFS in multivariate analysis (hazard ratio, 0.472; 95% confidence interval, 0.250–0.890; P=0.020). Conclusions: After 6 cycles of XELOX chemotherapy, capecitabine maintenance significantly prolonged PFS compared with observation, and toxicity was manageable. Maintenance treatment was a significant prognostic factor associated with PFS. [ABSTRACT FROM AUTHOR]

Background and Objective: In general, there are not many studies exploring the clinical value of adjuvant chemotherapy or maintenance chemotherapy (AC/MC) after induction chemotherapy and concurrent chemoradiotherapy (IC+CCRT+AC/MC). The purpose of this study was to establish a clinical nomogram for the use of AC/MC in patients with locoregionally advanced nasopharyngeal carcinoma (LA‐NPC). Material and Methods: Two centers (Guangzhou Medical University Cancer Center [N = 1226] and Zhongshan People's Hospital [N = 150]) recruited 1376 patients with LA‐NPC. All the patients underwent IC+CCRT; 560 patients received AC with cisplatin/nedaplatin plus docetaxel/paclitaxel (TP) or cisplatin/nedaplatin plus fluorouracil (PF), and 81 patients received MC with S‐1. Multivariate Cox regression was used to confirm optimal predictors of progression‐free survival (PFS), and a nomogram was established to identify patients into low‐risk and high‐risk cohorts. Additionally, bootstrap internal validation was performed to further verify our nomogram. Results: After propensity score matching (PSM), the survival curves were not statistically different between IC+CCRT+AC/MC and IC+CCRT (all p > 0.05). Then, a nomogram was developed based on variables that were screened by univariate and multivariate Cox regression, including N stage, cumulative platinum dose during CCRT, body mass index (BMI), IC cycles, IC regimen and cervical lymph node (CLN) necrosis and infiltration of adjacent tissues. The results of the nomogram showed that the high‐risk cohort had greatly worse 5‐year DMFS, LRFS, PFS and OS compared to low‐risk cohort (all p < 0.05), and subgroup analysis found that the 5‐year DMFS, PFS and OS of patients treated with IC+CCRT+AC/MC were better than those treated with IC+CCRT in high‐risk cohort (all p < 0.05). Notably, the incidence of adverse effects for IC+CCRT+AC cohort was higher than that for IC+CCRT+MC cohort, especially leukocytopenia and neutropenia. IC+CCRT and IC+CCRT+MC were associated with similar incidences of adverse effects. Conclusions: The addition of AC or MC to IC+CCRT could improve the DMFS of patients with high‐risk NPC and prolong their survival. Additionally, our findings suggest a potential role of AC/MC following IC plus CCRT in the treatment of high‐risk LA‐NPC. [ABSTRACT FROM AUTHOR]

Bendamustine (B) with rituximab (R) is a standard frontline treatment for medically fit follicular lymphoma (FL) patients. The safety and efficacy of maintenance rituximab (MR) after BR induction has not been formally compared to observation for FL, resulting in disparate practice patterns. Prospective trials have shown benefit of MR after R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or R-CVP (rituximab, cyclophosphamide, vincristine, prednisone), yet recent data from the GALLIUM study comparing outcomes of patients treated with chemotherapy with R or obinutuzumab (G) showed higher than anticipated fatal adverse events with BR/BG. In order to assess the efficacy and tolerability of MR after BR, we retrospectively collected data on 640 newly diagnosed patients treated with FL. We found that patients who achieved partial remission (PR) after ≥4 cycles of BR had improved duration of response (DOR) with MR vs. no maintenance, whereas those in complete remission did not. These findings were confirmed in a validation cohort. In the entire study population, the known fatal adverse event rate after BR was 2·5% and did not significantly differ in those receiving MR versus no maintenance. [Correction added on 14 January 2019, after online publication: The preceding sentence has been corrected in this current version.] Within the limitations inherent to retrospective analysis, these data suggest that FL patients with a PR to BR experience prolongation of remission with MR with an acceptable safety profile.

PurposeRecent data indicate consolidative radiation therapy improves progression-free survival (PFS) for patients with oligometastatic non-small cell lung cancer (NSCLC). Data on long-term outcomes are limited.Methods and materialsThis prospective, multicenter, single-arm, phase 2 trial was initiated in 2010 and enrolled patients with oligometastatic NSCLC. Oligometastatic disease was defined as a maximum of 5 metastatic lesions for all disease sites, including no more than 3 active extracranial metastatic lesions. Limited mediastinal lymph node involvement was allowed. Patients achieving a partial response or stable disease after 3 to 6 cycles of platinum-based chemotherapy were treated with CRT to the primary and metastatic sites of disease, followed by observation alone. The primary endpoint was PFS, with secondary endpoints of local control, overall survival (OS), and safety.ResultsTwenty-nine patients were enrolled between October 2010 and October 2015, and 27 were eligible for consolidative radiation therapy. The study was closed early because of slow accrual but met its primary endpoint for success, which was PFS >6 months (P

High risk neuroblastoma (HRNB) accounts for 15% of all pediatric cancer deaths. Despite aggressive therapy approximately half of patients will relapse, typically with only transient responses to second-line therapy. This study evaluated the ornithine decarboxylase inhibitor difluoromethylornithine (DFMO) as maintenance therapy to prevent relapse following completion of standard therapy (Stratum 1) or after salvage therapy for relapsed/refractory disease (Stratum 2). This Phase II single agent, single arm multicenter study enrolled from June 2012 to February 2016. Subjects received 2 years of oral DFMO (750 ± 250 mg/m2 twice daily). Event free survival (EFS) and overall survival (OS) were determined on an intention-to-treat (ITT) basis. 101 subjects enrolled on Stratum 1 and 100 were eligible for ITT analysis; two-year EFS was 84% (±4%) and OS 97% (±2%). 39 subjects enrolled on Stratum 2, with a two-year EFS of 54% (±8%) and OS 84% (±6%). DFMO was well tolerated. The median survival time is not yet defined for either stratum. DFMO maintenance therapy for HRNB in remission is safe and associated with high EFS and OS. Targeting ODC represents a novel therapeutic mechanism that may provide a new strategy for preventing relapse in children with HRNB.

BackgroundIn the phase 3 SOLO2 trial (ENGOT Ov-21), maintenance therapy with olaparib tablets significantly prolonged progression-free survival (primary endpoint) compared with placebo in patients with a germline BRCA1 or BRCA2 (BRCA1/2) mutation and platinum-sensitive, relapsed ovarian cancer who had received two or more lines of previous chemotherapy. The most common subjective adverse effects included fatigue, nausea, and vomiting, which were typically low grade and self-limiting. Our a-priori hypothesis was that maintenance olaparib would not negatively affect health-related quality of life (HRQOL) and additionally that the prolongation of progression-free survival with olaparib would be underpinned by additional patient-centred benefits.MethodsIn SOLO2, 196 patients were randomly assigned to olaparib tablets (300 mg twice daily) and 99 to placebo. Randomisation was stratified by response to previous chemotherapy (complete vs partial) and length of platinum-free interval (>6-12 vs >12 months). The prespecified primary HRQOL analysis evaluated the change from baseline in the Trial Outcome Index (TOI) score during the first 12 months of the study. To be assessable, patients had to have an evaluable score at baseline and at least one evaluable follow-up form. Secondary planned quality-of-life (QOL) analyses included the duration of good quality of life (defined as time without significant symptoms of toxicity [TWiST] and quality-adjusted progression-free survival [QAPFS]). Efficacy and QOL outcomes were analysed in all randomly assigned patients (the full analysis set), and safety outcomes were analysed in all randomly assigned patients who received at least one dose of study drug. This ongoing study is registered with ClinicalTrials.gov, number NCT01874353, and is closed to new participants.FindingsThe adjusted average mean change from baseline over the first 12 months in TOI was -2·90 (95% CI -4·13 to -1·67) with olaparib and -2·87 (-4·64 to -1·10) with placebo (estimated difference -0·03; 95% CI -2·19 to 2·13; p=0·98). Mean QAPFS (13·96 [SD 10·96] vs 7·28 [5·22] months; difference 6·68, 95% CI 4·98-8·54) and mean duration of TWiST (15·03 [SD 12·79] vs 7·70 [6·42] months; difference 7·33, 95% CI 4·70-8·96) were significantly longer with olaparib than with placebo.InterpretationOlaparib maintenance therapy did not have a significant detrimental effect on HRQOL compared with placebo. There were clinically meaningful patient-centred benefits in both TWiST and QAPFS despite the adverse effects associated with olaparib. These patient-centred endpoints support the improvement in progression-free survival, the primary endpoint in SOLO2, and should be included in future trials of maintenance therapies.FundingAstraZeneca.

There is an unmet need for effective biological therapies for relapsed central nervous system (CNS) lymphoma. Lenalidomide is active in activated B-cell type diffuse large B-cell lymphoma and rituximab is effective in CNS lymphoma. These observations are the basis for this first trial of an immunomodulatory drug as monotherapy in CNS lymphoma, and, in patients with inadequate responses to lenalidomide, with rituximab. In an independent cohort, we evaluated lenalidomide maintenance after salvage with high-dose methotrexate or focal irradiation in relapsed primary CNS lymphoma (PCNSL). We determined safety, efficacy, and cerebrospinal fluid (CSF) penetration of lenalidomide at 10-, 15-, and 20-mg dose levels in 14 patients with refractory CD20+ CNS lymphoma. Nine subjects with relapsed, refractory CNS lymphoma achieved better than partial response with lenalidomide monotherapy, 6 maintained response ≥9 months, and 4 maintained response ≥18 months. Median progression-free survival for lenalidomide/rituximab was 6 months. In the independent cohort, response duration with lenalidomide maintenance after complete responses 2 through 5 were significantly longer than response durations after standard therapy. The CSF/plasma partition coefficient of lenalidomide was ≥20% at 15- and 20-mg dose levels. Change in CSF interleukin-10 at 1 month correlated with clinical response and response duration to lenalidomide. Metabolomic profiling of CSF identified novel biomarkers, including lactate, and implicated indoleamine-2,3 dioxygenase activity with CNS lymphoma progression on lenalidomide. We conclude that lenalidomide penetrates ventricular CSF and is active as monotherapy in relapsed CNS lymphomas. We provide evidence that maintenance lenalidomide potentiates response duration after salvage in relapsed PCNSL and delays whole brain radiotherapy (WBRT). This trial was registered at www.clinicaltrials.gov as #NCT01542918.

INTRODUCTION:3,4-diaminopyridine has been used to treat Lambert-Eaton myasthenia (LEM) for 30 years despite the lack of conclusive evidence of efficacy. METHODS:We conducted a randomized double-blind placebo-controlled withdrawal study in patients with LEM who had been on stable regimens of 3,4-diaminopyridine base (3,4-DAP) for ≥ 3 months. The primary efficacy endpoint was >30% deterioration in triple timed up-and-go (3TUG) times during tapered drug withdrawal. The secondary endpoint was self-assessment of LEM-related weakness (W-SAS). RESULTS:Thirty-two participants were randomized to continuous 3,4-DAP or placebo groups. None of the 14 participants who received continuous 3,4-DAP had > 30% deterioration in 3TUG time versus 72% of the 18 who tapered to placebo (P

PurposeTo assess the safety and efficacy of upfront treatment using bortezomib combined with standard radiation therapy (RT) and temozolomide (TMZ), followed by adjuvant bortezomib and TMZ for ≤24 cycles, in patients with newly diagnosed glioblastoma multiforme (GBM).Methods and materialsTwenty-four patients with newly diagnosed GBM were enrolled. The patients received standard external beam regional RT with concurrent TMZ beginning 3 to 6 weeks after surgery, followed by adjuvant TMZ and bortezomib for ≤24 cycles or until tumor progression. During RT, bortezomib was given at 1.3 mg/m2 on days 1, 4, 8, 11, 29, 32, 36, and 39. After RT, bortezomib was given at 1.3 mg/m2 on days 1, 4, 8, and 11 every 4 weeks.ResultsNo unexpected adverse events occurred from the addition of bortezomib. The efficacy analysis showed a median progression-free survival (PFS) of 6.2 months (95% confidence interval [CI] 3.7-8.8), with promising PFS rates at ≥18 months compared with historical norms (25.0% at 18 and 24 months; 16.7% at 30 months). In terms of overall survival (OS), the median OS was 19.1 months (95% CI 6.7-31.4), with improved OS rates at ≥12 months (87.5% at 12, 50.0% at 24, 34.1% at 36-60 months) compared with the historical norms. The median PFS was 24.7 months (95% CI 8.5-41.0) in 10 MGMT methylated and 5.1 months (95% CI 3.9-6.2) in 13 unmethylated patients. The estimated median OS was 61 months (95% CI upper bound not reached) in the methylated and 16.4 months (95% CI 11.8-21.0) in the unmethylated patients.ConclusionsThe addition of bortezomib to current standard radiochemotherapy in newly diagnosed GBM patients was tolerable. The PFS and OS rates appeared promising, with more benefit to MGMT methylated patients. Further clinical investigation is warranted in a larger cohort of patients.

Background: Anti-epidermal growth factor receptor therapy showed an overall median survival improvement in wild type Ras metastatic colorectal cancer. Maintenance with anti EGFR in metastatic colorectal cancer wild type Ras was studied in many trials with promising results and many of these trials gave combined chemo with the target therapy and this combination had shown benefit in the form of synergistic effect and in delaying the resistance to the anti EGFR ., Method: In our study patients received 6 cycles of 5-FU based chemotherapy with Panitumumab and patients who had partial response, complete response or stationary disease received metronomic Capecitabine with Panitumumab every 2 weeks for one year. The primary end point was progression free survival (PFS) and the secondary end points were safety, toxicity and overall survival (OS)., Results: The median PFS for all patients was 18 ± 1.4 months and the median OS was 45 months. Patients with synchronous metastasis and those who received Oxaliplatin based regimen with Panitumumab were found to have longer PFS compared to those with metachronous metastasis or those who received other chemotherapy regimen with accepted toxicity profile to the maintenance therapy., Conclusion: Using Panitumumab with metronomic Capecitabine is considered an accepted maintenance regimen in wild type Ras metastatic colorectal cancer regardless of the primary site.

Background: This ambispective study was designed to assess the efficacy and safety of avelumab maintenance in a real-world population of patients with metastatic urothelial cancer (UC)., Methods: Patients with metastatic UC and measurable disease that had not progressed following first-line platinum-based chemotherapy were treated with maintenance avelumab (800 mg administered every 2 weeks). The primary endpoint was overall survival (OS)., Results: A total of 110 patients were enrolled. The majority of patients were male (81%), with a median age of 65 years (range, 36-84). The median OS was not reached, with a 1-year OS rate of 78.7%. The median PFS was 9.5 months (95% CI, 7.8-11.2 months). The ORR to first-line chemotherapy was 48.2%, and an additional 34.6% of patients responded to avelumab therapy (16 complete and 22 partial responses). Grade 3 adverse events during avelumab therapy were experienced by 11.8% of patients., Conclusions: These findings demonstrate similar efficacy and safety of avelumab in a real-world setting when compared to data from pivotal study., Trial Registration: KCRB registry number: RAVE-Bladder., (© 2025 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background & Aims: Understanding placebo rates is critical for efficient clinical trial design. We assessed placebo rates and associated factors using individual patient data from Crohn's disease trials., Methods: We conducted a meta-analysis of phase 2/3 placebo-controlled trials evaluating advanced therapies in moderate to severe Crohn's disease (2010-2021). Deidentified individual patient data were obtained through Vivli Inc and the Yale University Open Data Access Project. Primary outcomes were clinical response and remission. Pooled placebo rates and 95% confidence intervals (CIs) were estimated using 1- and 2-stage meta-analytic approaches. Regression analyses identified patient-level factors associated with placebo rates., Results: Analysis of individual patient data from 8 induction (n = 1147) and 4 maintenance (n = 524) trials showed overall placebo clinical response and remission rates for induction were 27% (95% CI, 23%-32%) and 10% (95% CI, 8%-14%), respectively, and 32% (95% CI, 23%-42%) and 22% (95% CI, 14%-33%) for maintenance, respectively. Among biologic (bio)-naïve patients, placebo response and remission rates during induction were 29% (95% CI, 24%-35%) and 11% (95% CI, 8%-15%) respectively, and 26% (95% CI, 20%-33%) and 10% (95% CI, 8%-14%) for biologic (bio)-exposed patients, respectively. During maintenance, biologic-naïve response and remission rates were 41% (95% CI, 34%-48%) and 32% (95% CI, 24%-40%), respectively, and 29% (95% CI, 24%-34%) and 16% (95% CI, 13%-21%) for bio-exposed, respectively. Higher baseline C-reactive protein concentration predicted lower placebo rates, whereas higher baseline albumin levels and body mass index increased the odds of placebo outcomes. Increased baseline Crohn's Disease Activity Index and 2-item patient-reported outcome scores predicted higher response rates in induction, lower response rates in maintenance, and lower remission rates in induction and maintenance., Conclusions: Patient- and trial-level characteristics influence placebo rates in Crohn's disease trials. Careful implementation of eligibility criteria, outcome definitions, and patient stratification may reduce placebo rates., (Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.)

This case report highlights sorafenib as maintenance therapy postallogeneic hematopoietic stem cell transplantation (allo-HSCT) in a young patient with acute myeloid leukemia (AML) with FMS-like tirosine kinase-3 (FLT3)-internal tandem duplication (ITD) mutation. Given the high relapse risk in FLT3-ITD-positive AML, the tyrosine kinase inhibitor sorafenib was administered. Several studies have shown that sorafenib improves survival in younger AML patients when combined with chemotherapy, though side effects can limit use in older patients. Sorafenib is increasingly significant after allo-HSCT maintenance, offering a promising option for high-risk AML cases. In this case, the patient achieved long-term remission with minimal side effects., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The aim of this observational, retrospective, multicenter study (Epimetheo) was to analyze the activity and the safety of stereotactic body radiation therapy (SBRT) during poly(ADP-ribose)-polymerase inhibitor (PARPi) maintenance in a series of oligometastatic ovarian cancer (OC) patients., Methods and Materials: Patients treated with PARPi in maintenance setting received SBRT if oligometastatic progression occurred. Maintenance treatment was continued until the extensive progression of the disease. The primary endpoints of the study were as follows: next systemic treatment change-free survival (NEST-FS) and acute and late toxicity; the secondary endpoints were as follows: the rate of clinical complete response (CR), the 2-year actuarial local control (LC, progression of disease inside SBRT field) rate on "per lesion" basis, the 2-year actuarial progression-free survival, and 2-year overall survival (OS)., Results: From April 2018 to September 2023, SBRT was used to treat 74 OC patients with a total of 158 lesions (98 lymph nodes and 60 parenchymal lesions) under PARPi maintenance. Olaparib, niraparib, and rucaparib were administered to 41.9%, 48.6%, and 9.5% of patients, respectively. CR, partial response, stable disease, and progressive disease were observed in 115 (72.8%), 32 (20.3%), 9 (5.7%), and 2 lesions (1.3%), respectively. Severe toxicities were reported in less than 3% of patients. The actuarial median NEST-FS was 10 months, with a range of 6.7-13.3 months. The 12- and 24-month actuarial NEST-FS rates were 44.9% and 31.4%, respectively. The 2-year actuarial LC, progression-free survival, and OS were 68.1%, 22.5%, and 77%, respectively with differences in figures between complete and incomplete responders. The achievement of CR was found to be correlated with an improvement in LC and OS., Conclusions: This study reports the activity and the low toxicity profile of SBRT in association with PARPi in oligometastatic OC patients. A rapid, minimally invasive, and cost-effective treatment such as SBRT may be proposed as a means of prolonging NEST-FS and maintaining an effective treatment regimen involving PARPi., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Maintenance therapy following first-line chemotherapy is of particular significance in patients diagnosed with recurrent or metastatic nasopharyngeal carcinoma (NPC). We conducted a meta-analysis to investigate the impact of maintenance therapy (MT) on the survival prognosis of individuals with recurrent or metastatic NPC., Methods: The databases Embase, PubMed, and the Cochrane Library were thoroughly searched in a comprehensive manner. Prospective studies of MT for recurrent or metastatic NPC are required. Study endpoints included progression-free survival (PFS) and overall survival (OS)., Results: Two randomized controlled clinical trials, with a total of 294 participants, were analyzed. The maintenance therapy group consisted of 140 participants, while the remaining participants were in the non-maintenance therapy (non-MT) group. The MT group showed a notable enhancement in PFS compared to the non-MT group, with a hazard ratio(HR) of 0.44 and a 95% Confidence interval [CI] of 0.34-0.58 (p < 0.0001). Overall survival was also significantly improved (HR0.42, 95% CI 0.30-0.58; p < 0.0001). The incidence of grade 3 or 4 side effects in the MT group was leukopenia (2.9%), thrombocytopenia (0.7%), and anemia (4.3%), hand-foot syndrome (5.8%), and thrombocytopenia (0.7%). oral mucositis (1.5%), and nausea and vomiting (2.2%)., Conclusions: Maintenance therapy with S-1 (tegafur/gimeracil/oltiracetam) or capecitabine following first-line chemotherapy significantly enhanced OS and PFS in patients with recurrent or metastatic nasopharyngeal carcinoma, while exhibiting minimal incidence of grade 3-4 side effects., Competing Interests: Declarations. Ethical approval: This meta-analysis of existing literature does not require an ethics statement. Conflict of interest: The authors have no conflicts of interest to declare., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Abstract: No randomized trial has directly compared daratumumab and lenalidomide (D-R) maintenance with standard-of-care lenalidomide (R) alone after transplant. Herein, we report the primary results of the phase 3 AURIGA study evaluating D-R vs R maintenance in patients with newly diagnosed multiple myeloma (NDMM) who had very good or better partial response, were minimal residual disease (MRD)-positive (10-5) and anti-CD38-naïve after transplant. Two hundred patients were randomly assigned (1:1) to D-R (n = 99) or R (n = 101) maintenance for up to 36 cycles. The MRD-negative (10-5) conversion rate by 12 months from start of maintenance (primary end point) was significantly higher for D-R than R (50.5% vs 18.8%; odds ratio [OR], 4.51; 95% confidence interval [CI], 2.37-8.57; P < .0001). MRD-negative (10-6) conversion rate was similarly higher with D-R (23.2% vs 5.0%; OR, 5.97; 95% CI, 2.15-16.58; P = .0002). At median follow-up (32.3 months), D-R achieved a higher overall MRD-negative (10-5) conversion rate (D-R, 60.6% vs R, 27.7%; OR, 4.12; 95% CI, 2.26-7.52; P < .0001) and complete response rate or better (75.8% vs 61.4%; OR, 2.00; 95% CI, 1.08-3.69; P = .0255) vs R. Progression-free survival (PFS) favored D-R vs R (hazard ratio, 0.53; 95% CI, 0.29-0.97); estimated 30-month PFS rates were 82.7% for D-R and 66.4% for R. Incidences of grade 3/4 cytopenias (54.2% vs 46.9%) and infections (18.8% vs 13.3%) were slightly higher with D-R than R. In conclusion, D-R maintenance achieved a higher MRD-negative conversion rate and improved PFS after transplant vs R, with no new safety concerns. This trial was registered at www.clinicaltrials.gov as #NCT03901963., (© 2025 American Society of Hematology. Published by Elsevier Inc. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. In multiple myeloma (MM), measurable residual disease (MRD) is assessed in bone marrow (BM). However, less invasive evaluation of peripheral residual disease (PRD) in blood could be advantageous and less cumbersome. We investigated the prognostic value of PRD monitoring after 24 cycles of maintenance in 138 transplant-eligible patients with MM enrolled in the GEM2012MENOS65/GEM2014MAIN clinical trials. PRD was assessed using next-generation flow (NGF) and mass spectrometry (MS). Positive PRD by NGF in 16/138 (11.5%) patients was associated with a 13-fold increased risk of progression and/or death; median progression-free survival (PFS) and overall survival (OS) were 2.5 and 47 months, respectively. Considering patients' MRD status in BM as the reference, PRD detection using NGF showed positive and negative predictive values of 100% and 73%, respectively. Presence of PRD helped identifying patients at risk of imminent progression among those with positive MRD in BM. Patients with undetectable PRD according to both NGF and MS showed 2-year PFS and OS rates of 97% and 100%, respectively. In multivariate analyses including the Revised International Staging System and the complete remission status, only MRD in BM and PRD by NGF showed independent prognostic value for PFS. This study supports the use of less invasive PRD monitoring during maintenance or observation in transplant-eligible patients with MM.

Patients with relapsed or refractory (r/r) acute myeloid leukemia (AML) have very poor long-term outcomes. Allogeneic stem cell transplantation (allo-SCT) can potentially cure some of these patients who are able to achieve a second or greater remission with salvage chemotherapy. Unfortunately, several barriers exist to transplantation and not all patients with r/r AML are able to proceed to allo-SCT. Therefore, novel therapies to decrease the risk of relapse in these patients are urgently needed. Wilms tumor 1 (WT1) protein has emerged as an encouraging vaccine target in AML due to its overexpression in leukemic blast cells and near absence in normal hematopoietic cells. Maintenance therapy with galinpepimut-S, a multivalent heteroclitic WT1 peptide vaccine, holds promise in early phase trials, in patients with AML by inducing a strong innate immune response against the WT1 antigen, leading to the design of this international, open-label, randomized clinical trial, named REGAL. Clinical trial registration: https://clinicaltrials.gov/study/NCT04229979. The clinical trial identifier is NCT04229979.

Aims: To assess real-world progression-free survival (rwPFS) and time to next treatment (rwTTNT) among patients with epithelial ovarian cancer (EOC) who received first-line maintenance (1LM) niraparib monotherapy., Patients & Methods: In this US-nationwide, electronic health record-derived, deidentified database study, eligible patients with EOC initiated 1LM niraparib monotherapy (1 January 2017-1 December 2022) following first-line platinum-based chemotherapy. Median rwPFS and rwTTNT were estimated with Kaplan-Meier methodology overall and in a homologous recombination-deficient (HRd) subgroup (further stratified as BRCA wild-type [ BRCA wt] or BRCA -mutated [ BRCA m])., Results: Observed median rwPFS was 11.4 (95% CI, 10.1-12.7) months overall ( N  = 560), 18.2 (95% CI, 13.9-24.2) months for the HRd subgroup ( n  = 144), and 25.4 (95% CI, 15.9-not reached) and 14.2 (95% CI, 8.6-18.6) months for HRd patients with BRCA m and BRCA wt tumors, respectively. Observed median rwTTNT was 12.4 (95% CI, 11.5-13.8) months overall, 19.6 (95% CI, 14.9-23.9) months for the HRd subgroup, and 24.9 (95% CI, 16.0-not reached) and 15.1 (95% CI, 10.3-19.8) months for HRd patients with BRCA m and BRCA wt tumors, respectively., Conclusions: The real-world observed median rwPFS and rwTTNT were longer for patients with EOC who received 1LM niraparib monotherapy in the HRd subgroup (specifically for the BRCA m subgroup).

Background: Small cell lung cancer is sensitive to chemotherapy and radiotherapy, but local recurrence and distant metastasis occur shortly after treatment. This study aimed to evaluate the real-world value of anlotinib as a maintenance therapy in patients with extensive-stage small cell lung cancer (ES-SCLC) after first-line chemotherapy and consolidative thoracic radiotherapy (CTRT)., Patients and Methods: A total of 150 patients with ES-SCLC treated with first-line chemotherapy and CTRT from April 2017 to December 2021 were retrospectively analyzed. After the completion of chemoradiotherapy, patients received anlotinib according to their desire. The primary endpoints were progression-free survival (PFS) and overall survival (OS) after the first diagnosis, and the secondary endpoints were prognostic factors and safety., Results: The ORR and DCR of patients with ES-SCLC were 50.0% and 80.3%, respectively, in the anlotinib group and 42.9% and 69.0% in the no-maintenance therapy group. The 3-year OS rates were 27.6% and 12.6% in the anlotinib and observation groups (HR = 2.52, P  = 0.003), and the median OS times were 23.8 months and 15.3 months. The 3-year PFS rates were 18.2% and 8.8% in the anlotinib and observation groups (HR = 1.76, P  = 0.034) with median PFS times of 11.5 months and 8.8 months. After stratification on the basis of clinical response, patients who achieved CR plus PR after chemoradiotherapy had a longer median OS in the anlotinib and observation groups (34.0 months vs 24.8 months, HR = 2.40, P  = 0.009). There were higher incidence rates of hand-foot syndrome (27.3% vs 10.5%, P  = 0.001), gingival bleeding/hemoptysis (18.5% vs 4.8%, P  = 0.015) and rash (33.3% vs 4.8%, P  < 0.001) in the anlotinib group than in the observation group., Conclusion: Maintenance therapy with anlotinib improved the survival of patients with ES-SCLC after first-line chemotherapy and CTRT. Owing to the small sample size of the real-world trial, the reliability of our study needs to be confirmed in more studies., 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.

Introduction: Malignant rhabdoid tumor (MRT) is a highly aggressive disease, mainly affecting infants and small children., Material and Methods: Between January 2007 and May 2021 a retrospective study was conducted at the Hospital de Pediatría J. P. Garrahan in Buenos Aires, Argentina, including 13 patients diagnosed with ERNC-MRT (extra-renal non-cerebral malignant rhabdoid tumor). Event-free survival (EFS) and overall survival (OS) were assessed using the Kaplan-Meier method and compared using the log-rank test., Results: Seven patients were less than 1 year old, all of them died. Four of 13 had metastatic disease, all of them in the lungs, 2 had locoregional lymph node involvement. Six achieved complete remission, 4 of them remained alive. Five received maintenance therapy (MT) with cyclophosphamide/vinorelbine, 4 were alive at last follow-up. Only one was studied for germline mutations, the result was negative. With a median follow-up of 126 months (range: 72-161), 3 and 5-year EFS and OS were 30.7% and 38.4%, respectively., Discussion: Although the sample size is small, survival rates are similar or slightly lower than other series. Age was the main prognostic factor. All but one patient that received MT are alive, suggesting that MT might have a role in ERNC-MRT; however, the prognostic significance is not entirely clear since there are multiple confounding factors.

For patients with acute myeloid leukaemia (AML) who achieve complete remission (CR) after induction therapy, subsequent allogeneic haematopoietic stem cell transplantation (allo-HSCT) reduces the risk of relapse. However, not all patients are eligible, warranting effective alternative maintenance strategies. Oral azacitidine is the only non-targeted therapy approved by both the United States (US) Food and Drug Administration and the European Medicines Agency for the maintenance or continued treatment of allo-HSCT-ineligible patients with AML achieving CR or CR with incomplete haematological recovery following induction chemotherapy. Midostaurin and histamine dihydrochloride are approved in Europe as maintenance therapy for AML in remission, and quizartinib is approved in the United States and Europe for the treatment and maintenance of patients with newly diagnosed FLT3-ITD AML. Barriers to maintenance treatment include limited clinical trial data informing appropriate patient and treatment selection, patient preference, financial burden and paucity of real-world data. This article discusses current maintenance treatment guidelines for patients with AML in remission but not proceeding to allo-HSCT and reviews clinical trial data for agents approved for use in remission. Ongoing studies of interest and considerations for future efforts are also discussed., (© 2024 The Author(s). British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Purpose: To evaluate atezolizumab combined with platinum-based chemotherapy (CT) followed by maintenance niraparib for late-relapsing recurrent ovarian cancer., Methods: The multicenter placebo-controlled double-blind randomized phase III ENGOT-OV41/GEICO 69-O/ANITA trial (ClinicalTrials.gov identifier: NCT03598270) enrolled patients with measurable high-grade serous, endometrioid, or undifferentiated recurrent ovarian cancer who had received one or two previous CT lines (most recent including platinum) and had a treatment-free interval since last platinum (TFIp) of >6 months. Patients were stratified by investigator-selected carboplatin doublet, TFIp, BRCA status, and PD-L1 status in de novo biopsy and randomly assigned 1:1 to receive either atezolizumab or placebo throughout standard therapy comprising six cycles of a carboplatin doublet followed (in patients with response/stable disease) by maintenance niraparib until progression. The primary end point was investigator-assessed progression-free survival (PFS) per RECIST v1.1., Results: Between November 2018 and January 2022, 417 patients were randomly assigned (15% BRCA- mutated, 36% PD-L1-positive, 66% TFIp >12 months, 11% previous poly [ADP-ribose] polymerase inhibitor after frontline CT, and 53% previous bevacizumab). Median follow-up was 28.6 months (95% CI, 26.6 to 30.5 months). Atezolizumab did not significantly improve PFS (hazard ratio, 0.89 [95% CI, 0.71 to 1.10]; P = .28). Median PFS was 11.2 months (95% CI, 10.1 to 12.1 months) with atezolizumab versus 10.1 months (95% CI, 9.2 to 11.2 months) with standard therapy. Subgroup analyses generally showed consistent results, including analyses by PD-L1 status. The objective response rate (ORR) was 45% (95% CI, 39 to 52) with atezolizumab and 43% (95% CI, 36 to 49) with standard therapy. The safety profile was as expected from previous experience of these drugs., Conclusion: Combining atezolizumab with CT and maintenance niraparib for late-relapsing recurrent ovarian cancer did not significantly improve PFS or the ORR.

Introduction: Multiple myeloma (MM) is an uncontrolled plasma cell proliferation in the bone marrow, leading to immune dysregulation with impaired humoral immune responses. Conversely, cellular-based responses play a vital role in MM patients. However, the extent and duration of cellular-induced protection remain unclear to date. Here, immunomodulatory drugs (IMiDs) like Lenalidomide (Lena) become interesting, as they may have stimulatory effects on T-cell functioning., Methods: In this study we investigated immune responses elicited by COVID-19 vaccine or infection comparing 43 healthy volunteers (avg. 35y, 72.1% female, 81.4% previously COVID-19 infected), with 41 MM patients under Lena maintenance therapy (avg. 63.8y, 51.2% female, 61% previously COVID-19 infected). Humoral responses to SARS-CoV-2 spike (S), spike-RBD, and nucleocapsid (N) were measured via ELISA in subjects' plasma. Freshly isolated PBMCs, incubated with SARS-CoV-2 peptides (N, S), activation induced marker (AIM) assays and flow cytometry, allowed us to assess cellular responses (CD8 + T, T (F)H : CD4 + T (follicular) helper)., Results: Whereas healthy controls showed significant better humoral responses (N IgA p<0.001), T cell responses were robust in the MM group (higher S-act. T H , p<0.001). Stratified by COVID-19 status, the MM group showed higher N-act. T H (p=0.03). These results were unchanged comparing a Lena intake with Lena break around vaccination., Discussion: Taken together, MM patients under Lena therapy exhibit weakened antibody production but present a robust T cell response following SARS-COV-2 infection or vaccination. Our results highlight the importance of vaccination in this subgroup and moreover, argue against a Lena intake break around the time of vaccination., Competing Interests: The 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Martac, Beer, Schenk, Ahmad, Maier, Demirel, Preuß, Klein, Stanger, Besemer, Hensen and Lengerke.)

Objective: In the phase 2 OVARIO trial (NCT03326193) investigating niraparib-bevacizumab first-line maintenance, median progression-free survival was 14.2 months (95% confidence interval (CI) 8.6 to 16.8) for patients with homologous recombination (HR)-proficient (HRp) epithelial ovarian cancer, and 12.1 months (95% CI8.0-not evaluated) for patients with undefined HR status. However, real-world data are limited for patients who receive niraparib-bevacizumab first-line maintenance therapy. The COMB1NE study describes real-world clinical outcomes (time to treatment discontinuation; time to next treatment) in patients with epithelial ovarian cancer who received niraparib-bevacizumab first-line maintenance, regardless of first-line bevacizumab use., Methods: This real-world, retrospective study used a US nationwide electronic health record-derived deidentified database. Eligible patients were 18 years or older at initial epithelial ovarian cancer diagnosis and initiated niraparib-bevacizumab first-line maintenance (January 1, 2017-September 2, 2022) following first-line treatment. The index date was the start of first-line maintenance. Patients were followed until death, last clinical activity, or end of study, whichever occurred first. Time to treatment discontinuation and time to next treatment, a proxy for real-world progression-free survival, were estimated using the Kaplan-Meier method., Results: Among 59 included patients, the median age was 67 years (interquartile range (IQR) 61-76), and 81.4% had stage III/IV epithelial ovarian cancer at diagnosis. Overall, 83.1% of patients had BRCA wild-type with either HRp or HR status unknown disease. Median time to treatment discontinuation of first-line maintenance was 11.8 months (95% CI 8.7 to 13.5). Median time to next treatment was 14.1 months (95% CI 11.3 to 16.6). At 6 months after index, 77.9% of patients had not initiated second-line treatment; at 12 months, 61.3% had not., Conclusion: In this real-world study of patients receiving niraparib-bevacizumab first-line maintenance, the majority of whom had HRp/HR status unknown, the median time to next treatment was consistent with observed progression-free survival in patients with similar HR status in the OVARIO study., Competing Interests: Competing interests: PHT has served on advisory boards for Aadi Pharmaceuticals, Agenus, AstraZeneca, Clovis Oncology, Eisai, GSK, ImmunoGen, Iovance, Merck, Mersana, Novocure, R-Pharm, Seagen, Imunon, Verastem, and Zentalis and has received grants from GSK and Merck. TACB, SB, JL, JH, LVK, JMS, JAH, and AKG are all employees of GSK and may hold stock in GSK., (© IGCS and ESGO 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Background: Signet ring cell carcinoma(SRCC)is a poorly prognostic cancer that primarily arises in the stomach. Its occurrence in the colon is extremely rare, with an incidence rate of 1%. We encountered a case of signet ring cell carcinoma that was considered to originate from the cecum based on clinical course and imaging findings., Case: A 69-year-old male had experienced abnormal bowel movements since last year and noticed abdominal distension since this year. He was referred to our hospital for further examination and treatment after a colonoscopy by a previous physician was difficult to perform. Physical examination revealed no abdominal distension or tenderness. Blood tests showed a mildly elevated tumor marker, with CEA at 5.5 ng/mL. Abdominal CT revealed stenosis centered on the terminal ileum with small bowel dilation. An ileus tube was placed the same day, and ileus tube imaging confirmed the stenosis of the terminal ileum. Diagnostic laparoscopy showed extensive peritoneal dissemination causing small bowel and sigmoid colon stenosis, and the ileocecal region was thickened and firmly adhered to the abdominal wall. Resection of the ileocecal region was deemed difficult, so a small bowel resection and ileostomy were performed. No other primary lesions were detected on imaging. Pathological examination of the ileal lesion revealed moderately to poorly differentiated adenocarcinoma/signet ring cell carcinoma primarily in the subserosal and muscular layers, suggesting cecal cancer with small bowel invasion and peritoneal dissemination. Genetic testing showed RAS wild-type, BRAF V600E wild-type, MSI negative, and HER2 negative. Chemotherapy (FOLFOX+Bmab)was initiated. Due to peripheral neuropathy and neutropenia, the dosage was reduced to 80% from the 6th course, but a total of 7 courses were administered. The patient has been free from disease progression for 8 months since the initial diagnosis., Conclusion: We experienced a case of cecal cancer with peritoneal dissemination accompanied by signet ring cell carcinoma, where maintenance chemotherapy proved effective.

Introduction: In JAVELIN Bladder 100, avelumab first-line maintenance (1LM) improved overall survival (OS) and progression-free survival (PFS) in patients with locally advanced/metastatic urothelial carcinoma (la/mUC) without progression following 1L platinum-based chemotherapy (PBC) versus best supportive care. PATRIOT-II describes real-world outcomes with avelumab 1LM., Patients and Methods: This observational, retrospective study of avelumab 1LM in US community/academic centers used medical record data collected from avelumab initiation for ≥12 months to assess survival, safety, and healthcare resource utilization; analyses are descriptive., Results: The study included 160 patients from 37 centers (median age, 70 years; 77% male). Avelumab 1LM was initiated at a median of 4 weeks (IQR 3-6) after PBC completion. Median follow-up from avelumab 1LM was 16 months (IQR 11-21). At study end, 19.4% of patients continued avelumab; 73.7% had discontinued due to progression, adverse events (AEs), or performance status deterioration. Median PFS and OS from avelumab initiation were 5.4 months (95% CI, 3.8-6.9) and 24.4 months (95% CI, 20.4-28.4), respectively. Grade ≥3 treatment-related AEs (TRAEs) occurred in 15 patients (9.4%); 35 (21.9%) had any-grade immune-related AEs, and 23 (14.3%) received high-dose systemic corticosteroids for AEs. Forty-four patients (27.5%) were hospitalized during the avelumab treatment period, of whom 13 (8.1%) were hospitalized due to TRAEs. Limitations of this study include a small sample size, potential selection bias, and missing/unknown data., Conclusion: These results align with the JAVELIN Bladder 100 clinical trial and other real-world studies, supporting avelumab 1LM use in patients with la/mUC without progression following 1L PBC., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Given the poor outcomes for peripheral T-cell lymphomas (PTCL), stem cell transplant (SCT) remains an important therapeutic approach. Post-SCT relapse is common and maintenance therapy post-SCT is increasingly being utilized. Here we review the use of post-SCT maintenance therapy for PTCL patients., Recent Findings: Maintenance therapy is increasingly utilized to decrease post-SCT relapse and improve outcomes in PTCL. Ongoing and completed post-SCT maintenance trials utilizing agents such as romidepsin, brentuximab vedotin, duvelisib, and pembrolizumab have shown efficacy in decreasing relapse. Further, additional agents with efficacy in PTCL have emerged that may inform future maintenance approaches. Maintenance therapy is a promising approach to maintain response after SCT in PTCL. While several trials are ongoing to evaluate maintenance therapy in PTCL, current data suggests this may be an effective method to decrease post-SCT relapse., Competing Interests: Declarations Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors. Conflict of Interest JEB: BMS/Celgene (research funding), Incyte (research funding), Verastem (advisory board), Valemetostat (advisory board)., (© 2024. The Author(s).)

Background: Paclitaxel plus ramucirumab is recommended as a second-line treatment regimen in patients with advanced HER2-negative gastric or gastro-oesophageal junction cancer. We aimed to assess whether switch maintenance or early second-line therapy with paclitaxel plus ramucirumab improved outcomes compared with continuation of oxaliplatin and fluoropyrimidine doublet chemotherapy as a first-line strategy., Methods: ARMANI was a multicentre, open-label, randomised, phase 3 trial done in 31 hospitals in Italy. We enrolled patients aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1 and locally advanced unresectable or metastatic HER2-negative gastric or gastro-oesophageal junction cancer, who had disease control after 3 months of FOLFOX (leucovorin, fluorouracil, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin). Patients were randomly assigned (1:1) to either paclitaxel 80 mg/m 2 on days 1, 8, and 15 plus ramucirumab at 8 mg/kg on days 1 and 15 every 28 days intravenously (switch maintenance group) or continuation of oxaliplatin-based doublet chemotherapy (FOLFOX or CAPOX) for an additional 12 weeks, followed by fluoropyrimidine monotherapy maintenance (control group). Randomisation was stratified by previous gastrectomy (no vs yes), peritoneal carcinomatosis (yes vs no), and primary tumour location (gastro-oesophageal junction vs gastric). Treatment group allocation was done using a web-based system with a minimisation algorithm implementing a random component. The primary endpoint was progression-free survival, analysed on an intention-to-treat basis. The safety population included patients who received at least one dose of the study treatment. This study is registered with ClinicalTrials.gov, NCT02934464, and is complete., Findings: Between Jan 1, 2017, and Oct 2, 2023, 280 patients were randomly assigned to receive paclitaxel plus ramucirumab (switch maintenance group; n=144) or to continue FOLFOX or CAPOX (control group; n=136). All patients were White. 180 (64%) of 280 patients were male and 100 (36%) were female. At a median follow-up of 43·7 months (IQR 24·0-57·9), 253 (90%) of 280 patients had a progression-free survival event: 131 (91%) of 144 patients in the switch maintenance group and 122 (90%) of 136 patients in the control group. Median progression-free survival was 6·6 months (95% CI 5·9-7·8) in the switch maintenance group and 3·5 months (2·8-4·2) in the control group (HR 0·61, 95% CI 0·48-0·79; p=0·0002). The assumption of proportional hazards was violated; in an analysis of 24-month restricted mean survival time, restricted mean progression-free survival was 8·8 months (95% CI 7·7-9·9) in the switch maintenance group and 6·1 months (5·0-7·2) in the control group (p=0·0010). The most frequent grade 3-4 treatment-related adverse events were neutropenia (37 [26%] patients in the switch maintenance group vs 13 [10%] patients in the control group), peripheral neuropathy (eight [6%] vs nine [7%]) and arterial hypertension (nine [6%] vs none). Serious adverse events occurred in 28 (20%) of 141 patients in the experimental group and 15 (11%) of 135 patients in the control group; these events were treatment-related in two (1%) patients in the switch maintenance group (pulmonary embolism) and two (1%) patients in the control group (mucositis and anaemia). No treatment-related deaths occurred., Interpretation: Paclitaxel and ramucirumab switch maintenance could be a potential treatment strategy in patients with advanced HER2-negative gastric or gastro-oesophageal junction cancer who are not eligible for immunotherapy or targeted agents., Funding: Partly funded by Eli Lilly., Competing Interests: Declaration of interests SL reports participation in advisory boards for Amgen, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, GSK, Incyte, Lilly, Merck Serono, MSD, Servier, Takeda, Rottapharm, and Beigene; personal honoraria as invited speaker from Amgen, AstraZeneca, Bristol-Myers Squibb, Incyte, GSK, Lilly, Merck Serono, MSD, Pierre Fabre, Roche, and Servier; and research funding (to their institution) from Amgen, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Daichii Sankyo, Hutchinson, Incyte, Merck Serono, Mirati, MSD, Pfizer, Roche, and Servier. MF reports research funding (to their institution) from Roche, Astellas, and Diaceutics; personal honoraria as an invited speaker from Roche, Astellas, AstraZeneca, Lilly, Incyte, Bristol-Myers Squibb, Sanofi, Agilent, Merck Serono, Pierre Fabre, GSK, Novartis, and Amgen; and participation in advisory boards for Amgen, Astellas, Roche, Merck Serono, GSK, Novartis, and Janssen. EG reports payment or honoraria from Servier, Amgen, Viatris, Pierre Fabre, Daiichi Sankyo, and AstraZeneca and support for attending meetings from Servier, Roche, Ipsen, and Viatris. LF reports grants or contracts from MSD, Bristol-Myers Squibb, AstraZeneca, Incyte, BeiGene, Astellas, Daiichi Sankyo, and Roche; consulting fees from MSD, AstraZeneca, Incyte, Taiho Oncology, Servier, Daiichi Sankyo, Eli Lilly, and BeiGene; and payment or honoraria from Incyte, Bristol-Myers Squibb, Eli Lilly, AstraZeneca, and MSD. FDV reports consulting fees from Daiichi Sankyo and payment or honoraria from Servier, Amgen, Roche, Eli Lilly, Daiichi Sankyo, and AstraZeneca. AS reports honoraria (advisory board member or invited speaker) from AstraZeneca, MSD, Daiichi, Jazz Pharma, and Astellas. FG reports payments or honoraria from Servier, Amgen, Novartis, Lilly, Eisai, and Daichi Sankyo and support for attending meetings and travel from Lilly, Roche, Amgen, and Servier. FM reports honoraria from Pierre Fabre and Servier; research grants from Incyte (to their institution), and travel grants from Amgen and Pierre Fabre. MN reports travel expenses from AstraZeneca, speaker honoraria from Accademia della Medicina and Incyte; honoraria from Sandoz, Medpoint, Incyte, AstraZeneca, and Servier for editorial collaboration; and consultant honoraria from EMD Serono, Basilea Pharmaceutica, Incyte, MSD Italia, Servier, Astra Zeneca, and Taiho. AR reports honoraria for speaker bureau or advisory board participation from Servier and MSD. FiP repors receiving research funding (to their institution) from Lilly, Bristol-Myers Squibb, Incyte, AstraZeneca, Amgen, and Agenus; personal honoraria as an invited speaker from BeiGene, Daiichi Sankyo, Seagen, Astellas, Ipsen, AstraZeneca, Servier, Bayer, Takeda, Johnson & Johnson, Bristol-Myers Squibb, MSD, Amgen, Merck Serono, Pierre Fabre; and advisory or consultancy fees from Bristol-Myers Squibb, MSD, Amgen, Pierre Fabre, Johnson & Johnson, Servier, Bayer, Takeda, Astellas, GSK, Daiichi Sankyo, Pfizer, BeiGene, Jazz Pharmaceuticals, Incyte, Rottapharm, and Merck Serono. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

The prevalence of anti-CD20 monoclonal antibody (MoAb)-associated delayed-onset neutropenia (DON) varies between 8 and 27%. Despite the wide use of MoAbs as maintenance in follicular lymphoma (FL), data regarding DON occurrence and clinical consequences are limited. This study assessed DON prevalence, severity and risk factors in FL patients during maintenance. Data were retrieved from electronic medical records of FL patients treated at Rambam between 2006 and 2021. The maintenance cohort included 155 patients receiving 165 treatment courses; the non-maintenance cohort included 58 patients receiving 67 courses. Median time on maintenance was 1.81 ± 0.28 years. During maintenance, 23.2% of patients developed DON, with 13.8% experiencing at least one recurrent event. In the non-maintenance cohort, 29.3% developed DON, with 38.8% recurrence. Median time from maintenance initiation to the first neutropenic episode was 5 (1.25-12) months, whereas in the non-maintenance cohort, DON occurred earlier [1.9 (0.97-3.71) months; p = 0.06]. The only DON risk factors in patients on maintenance were induction with the obinutuzumab/bendamustine combination [odds ratio (OR): 4.546 (95%CI = 1.419-14.563); p = 0.011] or obinutuzumab maintenance [OR: 3.138 (95%CI = 1.23-7.94); p = 0.016]. In the non-maintenance cohort, such factors included ≥ 1 line of therapy [OR: 3.93 (95%CI = 1.00-15.38); p = 0.04] and a lower absolute neutrophil count at induction completion. Differences in the likelihood of DON development between patients receiving maintenance with obinutuzumab or rituximab possibly reflect mechanistic dissimilarities between type I and type II MoAbs. Regardless, prolonged MoAb use bears a mitigatory effect, reducing recurrence of DON. The findings obtained could assist in predicting the risk of DON in individual FL patients, optimizing informed treatment choices., Competing Interests: Declarations. Ethics Statement: All the procedures involved in this study were in accordance with the ethical standards of the. Institutional Review Board of the Rambam Health Care Campus (Approval # RMB-D-0227-21) and with the 1964 Helsinki Declaration and its later amendments. All the participants signed the Informed Consent Form. 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.)

Introduction: In cases of metastatic and unresectable urothelial carcinoma with no disease progression after 4 cycles of chemotherapy, including platinum agents, treatment options include continuation of chemotherapy or switching to maintenance therapy with avelumab. This study compared the treatment outcomes of avelumab maintenance therapy with those of pembrolizumab in urothelial carcinoma using propensity score matching., Patients and Methods: Between January 2017 and December 2022, 243 patients with metastatic and unresectable urothelial carcinoma were treated with either avelumab or pembrolizumab at the Yamaguchi University Hospital and its affiliated institutions. We retrospectively compared the oncological outcomes and adverse events by aligning patient characteristics and treatment backgrounds using propensity score matching., Results: The analysis compared 36 cases receiving avelumab maintenance therapy after chemotherapy to 49 cases where patients, after receiving 4 courses of chemotherapy including platinum-based agents without disease progression, were subsequently administered pembrolizumab as a second-line treatment following disease progression. Using propensity score matching, 27 cases from each group were selected for comparison. From the initiation of prechemotherapy to disease progression on immune checkpoint inhibitors, the median progression-free survival was 20.7 and 23.3 months in the avelumab and pembrolizumab groups, respectively, with no statistically significant difference observed (P = .358). However, avelumab tended to have a lower rate of high-dose glucocorticoid treatment compared to pembrolizumab., Conclusion: Progression-free survival was similar for avelumab maintenance therapy and the sequence of continued chemotherapy followed by pembrolizumab after no disease progression at four chemotherapy courses. Avelumab may require less high-dose glucocorticoid treatment, potentially enhancing safety., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Although olaparib has demonstrated substantial clinical benefits as maintenance therapy in BRCA mutation-carrying women with newly diagnosed advanced ovarian cancer, its effectiveness in patients without BRCA mutations remains poorly investigated. This study aims to provide the first evidence on the efficacy of mono-olaparib maintenance therapy in such context. Using real-world data from 11 high-volume tertiary care centers in China, a retrospective cohort study was conducted to assess the efficacy and safety of olaparib as first-line maintenance therapy in patients with BRCA wild-type ovarian cancer. The primary objective was 1-year progression-free survival rate. Safety was also evaluated. Fifty patients with a median age of 54 years were included, and all of them tested negative for BRCA mutations but positive for homologous recombination deficiency (HRD). The 1-year PFS rate was 75.2% (95% CI, 63.4 to 89.2), and the median PFS was 21.0 months (95% CI, 13.8 to 28.2). All the patients received olaparib at a starting dose of 300 mg twice daily, and none experienced serious adverse events (AEs). Eight (16%) patients had dose adjustment, but none discontinued olaparib treatment due to AEs. We provide the first evidence that mono-olaparib could be a safe and effective maintenance treatment option for patients newly diagnosed with HRD-positive/BRCA wild-type ovarian cancer., Competing Interests: Compliance with ethics guidelines. Conflict of interests Jing Li, Youguo Chen, Mian He, Xiaoxiang Chen, Hao Wen, Yu Kang, Kaijiang Liu, Ge Lou, Xipeng Wang, Qinglian Wen, Li Wang, and Zhongqiu Lin declare that they have no conflict of interest. The study was approved by the institutional review board at each center and the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Due to the retrospective nature of the study, written informed consent was waived., (© 2024. Higher Education Press.)

BackgroundRucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma.MethodsIn this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries. Eligible patients were aged 18 years or older, had a platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, had received at least two previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a cancer antigen 125 concentration of less than the upper limit of normal, had a performance status of 0-1, and had adequate organ function. Patients were ineligible if they had symptomatic or untreated central nervous system metastases, had received anticancer therapy 14 days or fewer before starting the study, or had received previous treatment with a poly(ADP-ribose) polymerase inhibitor. We randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28 day cycles using a computer-generated sequence (block size of six, stratified by homologous recombination repair gene mutation status, progression-free interval after the penultimate platinum-based regimen, and best response to the most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary outcome was investigator-assessed progression-free survival evaluated with use of an ordered step-down procedure for three nested cohorts: patients with BRCA mutations (carcinoma associated with deleterious germline or somatic BRCA mutations), patients with homologous recombination deficiencies (BRCA mutant or BRCA wild-type and high loss of heterozygosity), and the intention-to-treat population, assessed at screening and every 12 weeks thereafter. This trial is registered with ClinicalTrials.gov, number NCT01968213; enrolment is complete.FindingsBetween April 7, 2014, and July 19, 2016, we randomly allocated 564 patients: 375 (66%) to rucaparib and 189 (34%) to placebo. Median progression-free survival in patients with a BRCA-mutant carcinoma was 16·6 months (95% CI 13·4-22·9; 130 [35%] patients) in the rucaparib group versus 5·4 months (3·4-6·7; 66 [35%] patients) in the placebo group (hazard ratio 0·23 [95% CI 0·16-0·34]; p

Purpose: To investigate surgical and oncologic outcomes of secondary cytoreductive surgery for ovarian cancer recurrence, considering the exposure to previous first-line maintenance therapy., Methods: We retrospectively identified all women who underwent secondary cytoreductive surgery for ovarian cancer recurrence with cytoreductive intent at three Italian Gynecologic Oncology centers (1997-2022). Data on clinical, surgical, and pathological characteristics, neoadjuvant, adjuvant, and maintenance therapy, as well as follow-up information, were retrieved from prospectively collected databases and medical records., Results: We identified 189 patients. Maintenance therapy in the first-line setting was implemented in 108/189 (57 %) cases: bevacizumab in 77.7 % (84/108), PARP inhibitors (Olaparib, Niraparib, or Rucaparib) in 15.7 % (17/108), and bevacizumab + PARP-inhibitors in 4.6 % (5/108). Complete cytoreduction rate and perioperative complications in secondary surgery were not associated with previous maintenance therapy. Complete cytoreduction was achieved in 75 % (140/189) of patients, and any residual tumor was the strongest predictor of poor progression-free (Hazard ratio [HR] 3.91, 95 %CI 2.48-6.16) and cause-specific survival (HR 4.27, 95 %CI 2.36-7.70). First-line bevacizumab was independently associated with worse progression-free survival among patients with any residual tumor at secondary surgery. First-line PARP inhibitors were independently associated with worse progression-free and cause-specific survival regardless of complete cytoreduction. Second-line maintenance therapies were independently associated with better survival regardless of residual tumor after secondary surgery., Conclusion: Complete cytoreduction during secondary surgery for ovarian cancer recurrence is the strongest predictor of prognosis. First-line maintenance therapies do not appear to affect the safety and feasibility of secondary cytoreduction, although they may influence prognosis after secondary surgery., 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 © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.)