A Matching-Adjusted Indirect Comparison of Pembrolizumab + Chemotherapy vs. Nivolumab + Ipilimumab as First-Line Therapies in Patients with PD-L1 TPS ≥1% Metastatic NSCLC

SIMPLE SUMMARY: Pembrolizumab + chemotherapy and nivolumab + ipilimumab are approved first-line treatment options for patients with metastatic stage IV NSCLC with a PD-L1 tumor proportion score (TPS) ≥1%. Understanding the differences between these treatment options is required to inform clinical decision making. In the absence of head-to-head trials, this study indirectly compared the effectiveness of pembrolizumab + chemotherapy vs nivolumab + ipilimumab in this patient population by performing a matching-adjusted indirect comparison. Pembrolizumab + chemotherapy demonstrated clinical benefit compared to nivolumab + ipilimumab in patients with PD-L1 TPS ≥1% across multiple endpoints. Sub-group analyses in PD-L1 TPS ≥50% and 1–49% patients were consistent with results in the overall PD‑L1 TPS ≥1% population. This study provides important results to inform clinical decision making given the lack of head-to-head studies comparing pembrolizumab + chemotherapy and nivolumab + ipilimumab. ABSTRACT: Background: In the absence of head-to-head trials, this study indirectly compared the effectiveness of pembrolizumab + chemotherapy vs nivolumab + ipilimumab for the first-line treatment of metastatic stage IV NSCLC patients with PD-L1 tumor proportion score (TPS) ≥1%. Methods: An anchored matching-adjusted indirect comparison (MAIC) was conducted using pooled individual patient data (IPD) from the ITT population in KEYNOTE-021G, KEYNOTE-189 and KEYNOTE-407 (n = 816) and published aggregate data of nivolumab + ipilimumab from CheckMate 227 Part 1A (n = 793). To adjust for cross-trial differences in baseline characteristics, data from KEYNOTE-021G/KEYNOTE-189/KEYNOTE-407 were re-weighted to match the baseline characteristics of CheckMate 227 Part 1A. Outcomes included OS, PFS and ORR. Base case analyses were restricted to patients with PD-L1 TPS ≥1%, with sub-group analyses in PD-L1 TPS ≥50% and 1–49%. Results: The estimated HR (95% CI) of pembrolizumab + chemotherapy vs nivolumab + ipilimumab was 0.80 (0.59,1.09) and 0.53 (0.41,0.68) for OS and PFS, respectively. For ORR, the estimated risk ratio was 1.8 (1.3,2.4) for pembrolizumab + chemotherapy vs nivolumab + ipilimumab and the risk difference was 25.5% (15.0,36.0). PD-L1 TPS ≥50% and 1–49% sub-groups showed an OS HR of 0.89 (0.58,1.36) and 0.68 (0.46,1.01), respectively. Conclusion: These MAIC results suggest that pembrolizumab + chemotherapy leads to a greater clinical benefit vs nivolumab + ipilimumab in patients with PD-L1 TPS ≥1% across multiple endpoints.