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A total of 30 consecutive patients with refractory or relapsing non-Hodgkin's lymphoma (NHL) were treated with a combination of dexamethasone, etoposide (VP-16), ifosfamide, and cisplatin (DVIP). In all, 9 subjects (30%) showed a partial response and 10 (33%) achieved a complete response (CR) lasting from 2.5 to 24+ months. Aggressive histology, no prior therapy with VP-16, a CR to previous chemotherapy, and a treatment-free interval of greater than 6 months prior to the present study were associated with the high CR rate. DVIP caused pronounced myelosuppression (median granulocyte nadir and median platelet nadir, 380/mm3 and 73.000/mm3, respectively), but no drug-related death occurred. We conclude that DVIP is an effective salvage combination, especially in aggressive NHL, that produces acceptable toxicity. [ABSTRACT FROM AUTHOR] more...

Background/aim: In this observational study, we analyzed the time on treatment (ToT) and overall survival (OS) of patients with metastatic non-small cell lung cancer (mNSCLC) in a 2.7-million-member public health provider in Israel., Patients and Methods: Newly diagnosed patients with mNSCLC who initiated first-line tyrosine kinase inhibitor (TKI) therapy between Jan 2017-Dec 2020 were identified from the National Cancer Registry and Maccabi Healthcare Services database. Outcomes were assessed at a minimum of 23 months of follow-up (cutoff: 30th November 2022). All analyses compared first-line treatment osimertinib vs. standard TKIs (erlotinib, afatanib or gefitinib)., Results: A total of 165 patients (59% female, median age 68 years) were identified, including 58% smokers, 95% with adenocarcinomas, 33% with brain metastases, and 62%/15%/23% with 0-1/2-4/unknown performance status (PS). Of these, 77 (47%) were treated with standard TKI drugs and 88 (53%) with osimertinib as first-line treatment. The median duration of follow-up was 33.6 months (95%CI=29.9-37.3) and 58.5 months (95%CI=52.5-64.4) for patients who received osimertinib and standard TKIs, respectively. The median ToT (in months) was significantly (p<0.0001) longer with osimertinib (17.6; 95%CI=13.71-23.9) vs. standard TKIs (9.40; 95%CI=7.17-12.1). The 24-month survival rate was 58.0% among patients who received osimertinib and 50.6% among those who received standard TKI therapy (p=0.18). From second-line treatment initiation, 43.8% of those who received second-line osimertinib and 17.7% of those that received other second-line treatment were still alive at 24 months., Conclusion: Compared to standard TKIs, first-line osimertinib treatment was associated with a significantly longer ToT, and a longer OS. Our cohort also included patients with PS 2-4 who would not necessarily be included in clinical trials, allowing analysis of a real-world population., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.) more...

Introduction: In the phase 3 KEYNOTE-604 study (NCT03066778), pembrolizumab plus etoposide and platinum chemotherapy (EP) significantly ( p = 0.0023) improved progression-free survival versus placebo plus EP in previously untreated extensive-stage SCLC (ES-SCLC). We present health-related quality of life (HRQoL) results from KEYNOTE-604., Methods: Patients with stage IV SCLC were randomized 1:1 to pembrolizumab 200 mg or placebo every 3 weeks for 35 cycles plus four cycles of EP. Secondary end points included mean change from baseline to week 18 in the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 (QLQ-C30) global health status/quality of life (GHS/QoL) scale and time to deterioration in the composite outcome of cough, chest pain, or dyspnea from QLQ-C30 and QLQ-Lung Cancer Module 13. Two-sided, nominal p values are reported., Results: A total of 439 patients completed at least one QLQ-C30 and QLQ-Lung Cancer Module 13 assessment (pembrolizumab + EP, n = 221; placebo + EP, n = 218). GHS/QoL scores improved from baseline to week 18: least squares mean (95% confidence interval [CI]) changes were 8.7 (5.3-12.1) for pembrolizumab plus EP and 4.2 (0.9-7.5) for placebo plus EP. Between-group differences in least squares mean scores were improved for pembrolizumab plus EP (4.4 [95% CI: 0.2-8.7], p  = 0.040]). Median time to deterioration for the composite end point was not reached and 8.7 (95% CI: 5.9-not reached) months, respectively (hazard ratio = 0.80 [95% CI: 0.56-1.14], p  = 0.208)., Conclusions: First-line pembrolizumab plus EP therapy maintained HRQoL in patients with ES-SCLC and may be associated with greater improvement than placebo plus EP. Together with the efficacy and safety findings in KEYNOTE-604, HRQoL data support the benefit of pembrolizumab in ES-SCLC., (© 2023 The Authors.) more...

Introduction: ERBB2 or HER2 alterations are found in approximately 2% to 5% of NSCLCs; most are exon 20 insertion mutations. The efficacy and safety of poziotinib, an oral tyrosine kinase inhibitor, were assessed in patients with treatment-naive NSCLC whose tumors harbor HER2 exon 20 insertions., Methods: ZENITH20 is an open-label, multicohort, multicenter, global, phase 2 trial. ZENITH20-C4 enrolled treatment-naive patients with NSCLC with tumors harboring HER2 exon 20 insertions. Poziotinib was administered 16 mg once daily (QD) or 8 mg twice daily (BID). The primary end point was objective response rate (ORR) by independent central review. Secondary and exploratory end points included disease control rate, duration of response, progression-free survival, and safety., Results: A total of 80 patients (16 mg QD, n = 47; 8 mg BID, n = 33) were treated in ZENITH20-C4. ORR was 39% (95% confidence interval [CI]: 28%-50%; 31 of 80), with a disease control rate of 73% (95% CI: 61%-82%; 58 of 80); 80% of the patients experienced tumor reduction. Median duration of response was 5.7 (95% CI: 4.6-11.9) months, and median progression-free survival was 5.6 (95% CI: 5.4-7.3) months. The most common grade 3 treatment-related adverse events were rash (QD, 45%; BID, 39%), stomatitis (QD, 21%; BID, 15%), and diarrhea (QD, 15%; BID, 21%). Among all subtypes of HER2 exon 20 insertions, seven patients (9%) harboring tumors with G778&#95;P780dupGSP had the best clinical outcomes (ORR, 71%)., Conclusions: Poziotinib was found to have clinically meaningful efficacy with a manageable toxicity profile for patients with treatment-naive NSCLC harboring HER2 exon 20 mutations., (Copyright © 2023. Published by Elsevier Inc.) more...

Introduction: We investigated the associations among frailty, as determined via the comprehensive geriatric assessment (CGA), muscle measures (i.e., sarcopenia), and treatment-related toxicity in older adults with cancer in Israel., Materials and Methods: This prospective cohort study enrolled patients ≥65 years with newly-diagnosed stage IV lung, breast, or genitourinary cancer. Patients were enrolled and completed CGA before their first line of systemic therapy (chemotherapy, biologic therapy, immunologic therapy, or a combination thereof). CGA was used to classify patients as robust, pre-frail, or frail, and routine pre-treatment computed tomography (CT) images were used to quantify skeletal muscle index (SMI) and skeletal muscle density (SMD) at L3 cross-section. Two sarcopenia definitions were used: i. for women SMI <41 cm 2 /m 2 regardless of body mass index (BMI), and for men SMI <43 cm 2 /m 2 for those with BMI of <25 and < 53 cm 2 /m 2 for those with BMI ≥25; and ii. SMI <38 cm 2 /m 2 for women and < 41 cm 2 /m 2 for men, regardless of BMI. The associations between frailty and muscle measures with the occurrence of at least one adverse event (AE) grade ≥ 2 were examined using the chi-square test, and logistic regression to determine odds ratio (OR) and 95% confidence interval (CI)., Results: In total, 51 patients were included in the analysis. The median (interquartile range) age was 72 (68-76) years, 30 (59%) were male, and 26 (51%) had lung cancer. CGA data were available for 48 patients: fifteen (31%), thirteen (27%), and twenty (42%) were defined as robust, pre-frail, and frail, respectively. Overall, 33 (65%) were sarcopenic by the first aforementioned definition, and sixteen (31%) by the second. No statistically significant associations were identified between frailty and having at least one AE grade ≥ 2, or between frailty and sarcopenia. Statistically significant associations were found between having sarcopenia (the second definition) and having at least one AE grade ≥ 2 (P = 0.0217). The corresponding odds ratio (95% CI) was 4.2 (1.2-15.0), P = 0.026., Discussion: Our findings suggests that sarcopenia is significantly associated with treatment-related toxicity. Further studies with larger sample sizes are warranted., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.) more...

Introduction: Both pembrolizumab (P) as a monotherapy or in combination with platinum-based chemotherapy (PCT) represent standard first-line treatment options for advanced non-small cell lung cancer (aNSCLC) with PD-L1 tumor proportion score (TPS)≥50%. No predictive biomarkers exist to guide treatment decisions., Methods: 423 consecutive patients with EGFR/ALK/ROS1-wild-type PD-L1 TPS≥50% aNSCLC receiving P (n = 302) or PCT (n = 121) as a first-line treatment were identified in the electronic databases of 5 Israeli cancer centers. Overall survival (OS, months [mo]) was assessed in correlation with blood biomarkers (BB: NLR, dNLR, PLR, SII, LIPI, ALI); a predictive score was developed., Results: In the propensity score matching analysis (n = 236; 118 patients in each group matched for age, sex and ECOG PS), mOS was 17.2mo (95% CI, 13.2-36.5) and 21.3mo (95% CI, 14.8-NR) in groups P and PCT, respectively (P = .44). In group P, NLR, dNLR, PLR, LIPI, and ALI significantly correlated with OS in uni- and multivariate COX regression analyses (P < .05), whereas in group PCT, none of the BB demonstrated a significant correlation. A predictive score was developed (each parameter receiving one point): age≥65, female sex, never-smoking status, adenocarcinoma histology, dNLR≥3. In patients with predictive score 3-5, OS was significantly longer with PCT as compared to P: mOS NR (95% CI, 15.3-NR) and 8.7mo (95% CI, 5.8-13.7) (P = .0005), while OS didn't differ significantly in patients with predictive score 0-2 (P = .61)., Conclusion: With the limitations of the retrospective analysis, the proposed dNLR-based score appears to predict OS with P and PCT., (Copyright © 2021 Elsevier Inc. All rights reserved.) more...

Objectives: ALK inhibitors (ALKi) are the standard-of-care treatment for metastatic ALK-rearranged non-small cell lung cancer (NSCLC) in the first- and second-line setting. We conducted a real-world multi-institutional analysis, aiming to compare the efficacy of third-line ALKi versus chemotherapy in these patients., Methods: Consecutive ALK-positive metastatic NSCLC patients treated with at least one ALKi were identified in the working databases of 7 Israeli oncology centers (the full cohort). Demographic and clinical data were collected. Patients receiving any systemic treatment beyond 2 ALKi comprised the third-line cohort, whether a third ALKi (group A) or chemotherapy (group B). Groups A and B were compared in terms of overall survival (OS) and time-to-next-treatment line (TNT)., Results: At a median follow-up of 41 months (95% confidence interval [CI]: 32-55), 80 (47.1%) have died. Median OS (mOS) in the full cohort (n = 170) was 52 months (95% CI: 32-65). Number of ALKi (hazard ratio [HR] 0.765; 95% CI: 0.61-0.95; P = .024) and age (HR 1.02, 95% CI: 1.01-1.04, P = .009) significantly associated with OS in the full cohort. The third-line cohort included 40 patients, of which 27 were treated with third ALKi (group A) and 13 treated with chemotherapy (group B). mOS from third-line initiation was 27 months in group A (95% CI: 13-NR) and 13 months for group B (95% CI: 3-NR); the difference was not significant (NS; P = .12). Chemotherapy as first line (HR 0.17, 95% CI: 0.05-0.52, P = .002) and a higher number of ALKi (HR 0.38, 95% CI: 0.20-0.86, P = .011) associated significantly with longer OS of the third-line cohort. TNT was 10 months for group A (95% CI: 5-19) and 3 months for group B (95% CI: 0-NR); the difference was NS (P = .079)., Conclusion: We report mature real-world data of more than 4-year mOS in ALK-positive patients. The number of ALKi given was associated with a better outcome. OS and TNT demonstrated a statistically nonsignificant trend for a better outcome in patients receiving a third-line ALKi., (© The Author(s) 2022. Published by Oxford University Press.) more...

In advanced nonsmall cell lung cancer (aNSCLC), stopping nivolumab after 12 months negatively affects outcomes. We performed a world data-based analysis assessing the value of nivolumab continuation and optimal dosing beyond 24 months. Out of 697 consecutive patients with aNSCLC in whom nivolumab was initiated between 2015 and 2018, 45 patients receiving nivolumab for ≥24 months were selected. These were divided into Groups A: nivolumab administered at a dose 3 mg/kg q2 weeks/240 mg q2 weeks/480 mg q4 weeks, n = 25; B: nivolumab re-scheduled to a nonstandard dose 3 mg/kg q3 weeks-q8 weeks, n = 13; C: nivolumab stopped after 24 months, n = 7; (in Groups B and C-for reasons other than progressive disease or intolerable toxicity). Progression-free survival (PFS) (Revised Response Evaluation Criteria in Solid Tumors, version 1.1) and safety (Common Terminology Criteria for Adverse Events, version 4.03) were assessed. With median follow-up of 35.6 months (interquartile range 28.4-41.8), 4%, 31%, 29% and 30% of patients progressed in Groups A, B, C and B+C, respectively. PFS at 36 months since nivolumab initiation comprised 100%, 67%, 67% and 67%, in Groups A, B, C and B+C, respectively. PFS at 40 months since nivolumab initiation comprised 83%, 67%, 67% and 67%, in Groups A, B, C and B+C, respectively. Allocation to Group A vs Group B, C and B+C was associated with hazard ratio for PFS-0.20 (95% confidence interval [CI], 0.02-1.77, P-.15), 0.20 (95% CI, 0.02-2.25, P-.19) and 0.20 (95% CI, 0.02-1.66, P-.14), respectively. No differences in newly occurring or worsening adverse events between the groups were observed. A trend for worse PFS was observed with alternative nivolumab scheduling or quitting 24 months after initiation. Continuing nivolumab at a standard dose until disease progression or intolerable toxicity remains the standard treatment option., (© 2020 Union for International Cancer Control.) more...

Background: Little is known regarding the efficacy of immune checkpoint inhibitors (ICI) in patients with advanced large-cell neuroendocrine lung carcinoma (aLCNEC)., Methods: 125 consecutive patients with aLCNEC were identified in the electronic databases of 4 participating cancer centers. The patients were divided into group A (patients who received ICI, n=41) and group B (patients who did not receive ICI, n=84). Overall survival since advanced disease diagnosis (OS DX) and OS since ICI initiation (OS ICI) were captured., Results: With a median follow-up of 11.8 months (mo) (IQR 7.5-17.9) and 6.0mo (IQR 3.1-10.9), 66% and 76% of patients died in groups A and B, respectively. Median OS DX was 12.4mo (95% CI 10.7 to 23.4) and 6.0mo (95% CI 4.7 to 9.4) in groups A and B, respectively (log-rank test, p=0.02). For ICI administration, HR for OS DX was 0.59 (95% CI 0.38 to 0.93, p=0.02-unadjusted), and 0.58 (95% CI 0.34 to 0.98, p=0.04-adjusted for age, Eastern Cooperative Oncology Group (ECOG) performance status (PS), presence of liver metastases and chemotherapy administration). In a propensity score matching analysis (n=74; 37 patients in each group matched for age and ECOG PS), median OS DX was 12.5 mo (95% CI 10.6 to 25.2) and 8.4 mo (95% CI 5.4 to 16.9) in matched groups A and B, respectively (log-rank test, p=0.046). OS ICI for patients receiving ICI as monotherapy (n=36) was 11.0 mo (95% CI 6.1 to 19.4)., Conclusions: With the limitations of retrospective design and small sample size, the results of this real-world cohort analysis suggest a positive impact of ICI on OS in aLCNEC., Competing Interests: Competing interests: ED reported consulting fees from MSD, BMS, Astra Zeneca, Roche, Boehringer Ingelheim, Pfizer, Novartis, Takeda. MM reported consulting fees from Boehringer Ingelheim, Roche, Astra Zeneca, MSD, BMS, Abbvie, Takeda, Pomicell. CK reported research funding (to institution) from AstraZeneca, BMS, Novartis, Regeneron, Tesaro, Karyopharm, Debiopharm, Jassen, and Mirati and consulting fees from Novartis. SVL reported consulting fees from AstraZeneca, Beigene, Blueprint, Boehringer Ingelheim, Bristol-Myers Squibb, Catalyst, Celgene, Clovis, Corvus, G1 Therapeutics, Genentech, Guardant Health, Inivata, Janssen, Jazz, Lilly, LOXO, MSD, PharmaMar, Pfizer, Regeneron, and Takeda and research grants (to institution) from Alkermes, AstraZeneca, Bayer, Blueprint, Bristol-Myers Squibb, Genentech, Lilly, Lycera, Merck, Molecular Partners, Pfizer, Rain Therapeutics, RAPT, Spectrum, and Turning Point Therapeutics. DU reported consulting fees and non-financial support from BMS, Astra Zeneca, Takeda, consulting fees MSD, Roche and Boehringer Ingelheim. AZ reported grants from BMS, personal fees from Roche, MSD, BMS, Astra Zeneca, Takeda. AO reported advisory fees from MSD, BMS, Roche, Astra Zeneca, Novartis, Boehringer Ingelheim. MW reported speaker fees and funding (to institution) from Roche, MSD. JB reported grants and personal fees from MSD, Roche, BMS, Abbvie, Pfizer, Novartis, Astra Zeneca, Boehringer Ingelheim, Takeda., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.) more...