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ImportanceA key issue for the adjuvant treatment of patients with melanoma is the assessment of the effect of treatment on relapse, survival, and quality of life (QOL).ObjectiveTo compare QOL in patients with resected melanoma at high risk for relapse who were treated with adjuvant pembrolizumab vs standard of care with either ipilimumab or high-dose interferon α 2b (HDI).Design, Setting, and ParticipantsThe S1404 phase 3 randomized clinical trial was conducted by the SWOG Cancer Research Network at 211 community/academic sites in the US, Canada, and Ireland. Patients were enrolled from December 2015 to October 2017. Data analysis for this QOL substudy was completed in March 2022. Overall, 832 patients were evaluable for the primary QOL end point.InterventionsPatients were randomized (1:1) to treatment with adjuvant pembrolizumab vs standard of care with ipilimumab/HDI.Main Outcomes and MeasuresQuality of life was assessed for patients at baseline and cycles 1, 3, 5, 7, and 9 after randomization using the Functional Assessment of Cancer Therapy (FACT) Biological Response Modifiers (FACT-BRM), FACT-General, Functional Assessment of Chronic Illness Therapy–Diarrhea, and European QOL 5-Dimension 3-Level scales. The primary end point was the comparison by arm of cycle 3 FACT-BRM trial outcome index (TOI) scores using linear regression. Linear-mixed models were used to evaluate QOL scores over time. Regression analyses included adjustments for the baseline score, disease stage, and programmed cell death ligand 1 status. A clinically meaningful difference of 5 points was targeted.ResultsAmong 1303 eligible patients (median [range] age, 56.7 [18.3-86.0] years; 524 women [40.2%]; 779 men [59.8%]; 10 Asian [0.8%], 7 Black [0.5%], 44 Hispanic [3.4%], and 1243 White [95.4%] individuals), 1188 (91.1%) had baseline FACT-BRM TOI scores, and 832 were evaluable at cycle 3 (ipilimumab/HDI = 267 [32.1%]; pembrolizumab = 565 [67.9%]). Evaluable patients were predominantly younger than 65 years (623 [74.9%]) and male (779 [58.9%]). Estimates of FACT-BRM TOI cycle 3 compliance did not differ by arm (ipilimumab/HDI, 96.0% vs pembrolizumab, 98.3%; P = .25). The adjusted cycle 3 FACT-BRM TOI score was 9.6 points (95% CI, 7.9-11.3; P P P Conclusions and RelevanceThis secondary analysis of a phase 3 randomized clinical trial found that adjuvant pembrolizumab improved QOL vs treatment with adjuvant ipilimumab or HDI in patients with high-risk resected melanoma.Trial RegistrationClinicalTrials.gov identifier: NCT02506153

PURPOSE Resistance to immune checkpoint inhibition (ICI) in advanced non–small-cell lung cancer (NSCLC) represents a major unmet need. Combining ICI with vascular endothelial growth factor (VEGF)/VEGF receptor inhibition has yielded promising results in multiple tumor types. METHODS In this randomized phase II Lung-MAP nonmatch substudy (S1800A), patients ineligible for a biomarker-matched substudy with NSCLC previously treated with ICI and platinum-based chemotherapy and progressive disease at least 84 days after initiation of ICI were randomly assigned to receive ramucirumab plus pembrolizumab (RP) or investigator's choice standard of care (SOC: docetaxel/ramucirumab, docetaxel, gemcitabine, and pemetrexed). With a goal of 130 eligible patients, the primary objective was to compare overall survival (OS) using a one-sided 10% level using the better of a standard log-rank (SLR) and weighted log-rank (WLR; G[rho = 0, gamma = 1]) test. Secondary end points included objective response, duration of response, investigator-assessed progression-free survival, and toxicity. RESULTS Of 166 patients enrolled, 136 were eligible (69 RP; 67 SOC). OS was significantly improved with RP (hazard ratio [80% CI]: 0.69 [0.51 to 0.92]; SLR one-sided P = .05; WLR one-sided P = .15). The median (80% CI) OS was 14.5 (13.9 to 16.1) months for RP and 11.6 (9.9 to 13.0) months for SOC. OS benefit for RP was seen in most subgroups. Investigator-assessed progression-free survival (hazard ratio [80% CI]: 0.86 [0.66 to 1.14]; one-sided SLR, P = .25 and .14 for WLR) and response rates (22% RP v 28% SOC, one-sided P = .19) were similar between arms. Grade ≥ 3 treatment-related adverse events occurred in 42% of patients in the RP group and 60% on SOC. CONCLUSION This randomized phase II trial demonstrated significantly improved OS with RP compared with SOC in patients with advanced NSCLC previously treated with ICI and chemotherapy. The safety was consistent with known toxicities of both drugs. These data warrant further evaluation.