Tiragolumab Plus Atezolizumab and Chemotherapy for Advanced Nonsquamous Non-Small Cell Lung Cancer

Abstract

This randomized clinical trial evaluates the efficacy and safety of tiragolumab plus atezolizumab plus chemotherapy vs placebo plus pembrolizumab plus chemotherapy in patients with advanced nonsquamous non-small cell lung cancer.QuestionCan treatment with the combination of tiragolumab plus atezolizumab plus chemotherapy improve outcomes for patients with advanced nonsquamous non-small cell lung cancer (NSCLC)?FindingsIn this phase 3 randomized clinical trial of 542 patients with previously untreated, locally advanced unresectable or metastatic NSCLC, tiragolumab plus atezolizumab plus chemotherapy did not demonstrate a progression-free or overall survival benefit vs placebo plus pembrolizumab plus chemotherapy. Tiragolumab plus atezolizumab plus chemotherapy demonstrated a safety profile that was generally similar to that of pembrolizumab plus chemotherapy.MeaningTreatment with the combination of tiragolumab plus atezolizumab plus chemotherapy did not improve outcomes for patients with advanced nonsquamous NSCLC compared with pembrolizumab plus chemotherapy.ImportanceProgrammed cell death 1 ligand 1/programmed cell death protein 1 inhibitors, with or without chemotherapy, are standard first-line treatment for patients with advanced non-small cell lung cancer (NSCLC); however, survival benefit is limited, and many patients experience disease progression.ObjectiveTo evaluate the efficacy and safety of tiragolumab plus atezolizumab plus chemotherapy vs placebo plus pembrolizumab plus chemotherapy in patients with advanced nonsquamous NSCLC.Design, Setting, and ParticipantsSKYSCRAPER-06 was a phase 3 randomized clinical trial that recruited patients with previously untreated, locally advanced unresectable or metastatic NSCLC at 129 sites in 21 countries between December 15, 2020, and September 14, 2023 (data cutoff, April 19, 2024).InterventionPatients were randomized 1:1 to receive either tiragolumab, 600 mg, plus atezolizumab, 1200 mg, plus chemotherapy (pemetrexed, 500 mg/m2, and carboplatin [area under the curve 5], or cisplatin, 75 mg/m2) or placebo plus pembrolizumab, 200 mg, plus chemotherapy via intravenous infusion on day 1 of each 21-day cycle until disease progression, loss of clinical benefit, unacceptable toxic effect, or withdrawal of consent.Main Outcomes and MeasuresPrimary end points were investigator-assessed progression-free survival and overall survival. The safety and tolerability of the study drugs were also evaluated.ResultsOf 542 patients in the full analysis set (mean [SD] age, 63.6 [9.3] years; 353 [65.1%] male), 269 were randomized to tiragolumab plus atezolizumab plus chemotherapy and 273 to placebo plus pembrolizumab plus chemotherapy. Overall, baseline demographics were similar between treatment groups. At data cutoff (median follow-up, 11.8 months), median investigator-assessed progression-free survival was 8.3 months (95% CI, 7.1-9.6 months) with tiragolumab plus atezolizumab plus chemotherapy vs 9.9 months (95% CI, 8.7-11.9 months) with placebo plus pembrolizumab plus chemotherapy (hazard ratio, 1.27; 95% CI, 1.02-1.57; P = .99); median overall survival was 18.9 months (95% CI, 15.2-23.8 months) vs 23.1 months (95% CI, 20.7-33.0 months) in each treatment group, respectively (hazard ratio, 1.33; 95% CI, 1.02-1.73; P = .98). Grade 3 to 4 adverse events occurred in 164 of 267 patients (61.4%) in the tiragolumab plus atezolizumab plus chemotherapy group and 165 of 272 patients (60.7%) in the placebo plus pembrolizumab plus chemotherapy group, with grade 5 AEs occurring in 27 of 267 patients (10.1%) and 16 of 272 patients (5.9%) in each group, respectively.Conclusions and RelevanceIn the phase 3 SKYSCRAPER-06 randomized clinical trial, the primary end points were not met and the study has been terminated.Trial RegistrationClinicalTrials.gov Identifier: NCT04619797