MO01.20 Pembrolizumab+Chemo versus Atezolizumab+Chemo+/-Bevacizumab for First-Line Nonsquamous NSCLC: A Matching-Adjusted Indirect Comparison

Combination of chemotherapy and immunotherapy is widely used for treatment of advanced non-small cell lung cancer (NSCLC) without epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) aberrations. Pembrolizumab+chemotherapy, studied in KEYNOTE-021 Cohort G (KN021G) and KEYNOTE-189 (KN189), and atezolizumab+chemotherapy and atezolizumab+chemotherapy+bevacizumab, studied in IMpower 130 and IMpower 150, are all regulatory-approved regimens for nonsquamous NSCLC. Optimal choice with regards to the effectiveness between these regimens is not well-defined in the absence of head-to-head trial data. This study indirectly compared the effectiveness of pembrolizumab+chemotherapy versus atezolizumab+chemotherapy+/-bevacizumab for previously untreated non-squamous NSCLC patients without EGFR and ALK aberrations. A matching-adjusted indirect comparison (MAIC) was conducted using individual patient data (IPD) from KN021G (pembrolizumab+carboplatin+pemetrexed; N=59) and KN189 (pembrolizumab+pemetrexed+platinum chemotherapy; N=410) and published aggregated data from IMpower 130 (atezolizumab+carboplatin+nab-paclitaxel; N=451) and IMpower 150 (atezolizumab+carboplatin+paclitaxel+bevacizumab; N=356). Study designs and patient selection criteria were similar for all three trials. To adjust for cross-trial differences in baseline characteristics, data from patients randomized to pembrolizumab+chemotherapy in KN189/KN021G were re-weighted to match the baseline characteristics of patients randomized to atezolizumab+chemotherapy from IMpower 130 or atezolizumab+ chemotherapy+bevacizumab in IMpower 150. Due to the lack of common comparators between trials, an unanchored comparison was performed. Outcomes of interest 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. After adjusting 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 0.93 (0.81, 1.07) and -3% (-10.04, 3.14) for pembrolizumab+chemotherapy versus atezolizumab+chemotherapy, respectively, and 0.78 (0.67, 0.91) and -12% (-20, -5) for pembrolizumab+chemotherapy versus atezolizumab+chemotherapy+bevacizumab, respectively. Findings were consistent across sensitivity analyses for both outcomes. MAIC results showed a better OS and PFS effect with pembrolizumab+chemotherapy compared with atezolizumab+chemotherapy+/-bevacizumab. Given the lack of head-to-head studies comparing these regimens, results from these MAIC analyses may be useful to inform clinical practice and decision makers for prioritizing treatments.