Pembrolizumab+chemotherapy versus atezolizumab+chemotherapy+/−bevacizumab for the first-line treatment of non-squamous NSCLC: a matching-adjusted indirect comparison
Summary. Objectives. Several approved immunotherapy-chemotherapy combinations for the treatment of advanced non-small cell lung cancer (NSCLC) have not been directly compared in randomized clinical trials. This study aimed to conduct an indirect comparison of the efficacy of pembrolizumab plus chemotherapy versus atezolizumab plus chemotherapy, with or without bevacizumab, in previously untreated non-squamous NSCLC patients without EGFR/ALK aberrations. Materials and methods. A matching-adjusted indirect comparison (MAIC) approach was applied using individual patient data (IPD) from KEYNOTE-021 Cohort G (KN021 G) (pembrolizumab + carboplatin + pemetrexed; n=59) and KEYNOTE-189 (KN189) (pembrolizumab + pemetrexed + platinum-based chemotherapy; n=410). These data were compared with published aggregate data from IMpower 130 (atezolizumab + carboplatin + nab-paclitaxel; n=451) and IMpower 150 (atezolizumab + carboplatin + paclitaxel + bevacizumab; n=356). To adjust for baseline differences across studies, individual patient data from the pembrolizumab + chemotherapy arms (KN021 G/KN189) were reweighted to match the baseline characteristics of patients randomized to atezolizumab + chemotherapy (IMpower 130) or atezolizumab + chemotherapy + bevacizumab (IMpower 150). The study endpoints included overall survival (OS), progression-free survival (PFS) as assessed by blinded independent central review, and objective response rate (ORR). The follow-up duration for OS and PFS was aligned with the shortest follow-up period among the studies. A sensitivity analysis was performed without truncation of follow-up for 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 hazard ratios (HR) with 95% confidence intervals (CI) for OS and PFS with pembrolizumab + chemotherapy versus atezolizumab + chemotherapy were 0.80 (95% CI 0.67–0.95) and 0.79 (95% CI 0.67–0.93), respectively. When comparing pembrolizumab + chemotherapy with atezolizumab + chemotherapy + bevacizumab, the HRs (95% CI) were 0.86 (95% CI 0.72–1.03) for OS and 0.81 (95% CI 0.68–0.96) for PFS. For ORR, the relative risk (95% CI) and absolute risk difference (95% CI) between pembrolizumab + chemotherapy and atezolizumab + chemotherapy were 0.9 (95% CI 0.8–1.1) and −3.5% (95% CI −10.0 — −3.1%), respectively. When comparing pembrolizumab + chemotherapy with atezolizumab + chemotherapy + bevacizumab, the corresponding values were 0.8 (95% CI 0.7–0.9) and −12.2% (95% CI −19.6 — −4.8%). Sensitivity analyses confirmed the robustness of the findings across all evaluated endpoints. Conclusions. The results of this matching-adjusted indirect comparison suggest significantly improved OS and PFS with pembrolizumab + chemotherapy compared with atezolizumab + chemotherapy. Additionally, PFS was significantly higher with pembrolizumab + chemotherapy versus atezolizumab + chemotherapy + bevacizumab.
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