Pembrolizumab+chemotherapy versus atezolizumab+chemotherapy+/−bevacizumab for the first-line treatment of non-squamous NSCLC: A matching-adjusted indirect comparison

Objectives: Multiple immunotherapy and chemotherapy combinations are approved for the management of advanced NSCLC which have not been directly compared in randomized clinical trials. This study indirectly compared the effectiveness of pembrolizumab + chemotherapy versus atezolizumab + chemotherapy+/-bevacizumab for previously untreated non-squamous NSCLC patients without EGFR/ALK aberrations. Materials and methods: A matching-adjusted indirect comparison (MAIC) was conducted using individual patient data (IPD) from KEYNOTE-021 Cohort G (KN021 G) (pembrolizumab + carboplatin + pemetrexed; N = 59) and KEYNOTE-189 (KN189) (pembrolizumab + pemetrexed + platinum chemotherapy; N = 410) and published aggregate data from IMpower 130 (atezolizumab + carboplatin + nab-paclitaxel; N = 451) and IMpower 150 (atezolizumab + carboplatin + paclitaxel + bevacizumab; N = 356). To adjust for cross-trial differences in baseline characteristics, data from patients randomized to pembrolizumab + chemotherapy in KN021 G/KN189 were reweighted to match the baseline characteristics of patients randomized to atezolizumab + chemotherapy from IMpower 130 or atezolizumab + chemotherapy + bevacizumab from IMpower 150. Outcomes included overall survival (OS), blinded independent review-assessed progression-free survival (PFS) and objective response rate (ORR). OS and PFS follow-up were truncated to the trial with shorter follow-up. Sensitivity analyses were conducted without truncation of follow-up of OS and PFS. Results: After matching for cross-trial differences, the effective sample size of pembrolizumab + chemotherapy was 428 and 389 for the IMpower 130 and IMpower 150 comparisons, respectively. The estimated HRs (95 % CIs) of pembrolizumab + chemotherapy versus atezolizumab + chemotherapy were 0.80 (0.67,0.95) and 0.79 (0.67,0.93) with regard to OS and PFS, respectively. For pembrolizumab + chemotherapy versus atezolizumab + chemotherapy + bevacizumab, the estimated HR (95 % CIs) was 0.86 (0.72,1.03) for OS and 0.81 (0.68,0.96) for PFS. For ORR, the estimated risk ratio (95 % CI) and the risk difference (95 % CI) was 0.9 (0.8,1.1) and -3.5 % (-10.0,3.1) for pembrolizumab + chemotherapy versus atezolizumab + chemotherapy, respectively, and 0.8 (0.7,0.9) and -12.2 % (-19.6,-4.8) for pembrolizumab + chemotherapy versus atezolizumab + chemotherapy + bevacizumab, respectively. Findings were consistent across sensitivity analyses for both outcomes. Conclusion: MAIC results showed a significantly better OS and PFS for pembrolizumab + chemotherapy compared with atezolizumab + chemotherapy and a significantly better PFS for pembrolizumab + chemotherapy compared with atezolizumab + chemotherapy + bevacizumab.