P1.01-16 First-Line Pembrolizumab With or Without Chemotherapy in PD-L1 positive NSCLC: A Network Meta-Analysis of Randomized Trials

Abstract

Pembrolizumab has replaced platinum-doublet chemotherapy as first-line treatment for advanced non-small cell lung cancer (NSCLC) with tumor PD-L1 expression >/=50%. Among PD-L1 unselected patients, pembrolizumab + chemotherapy is superior to chemotherapy alone. This network meta-analysis compared pembrolizumab alone with pembrolizumab + chemotherapy in patients with >/=50% PD-L1 positive NSCLC. Using the Keynote 024 and 189 (PD-L1 >/=50% subgroup) trials, an indirect network was constructed to compare pembrolizumab and pembrolizumab + chemotherapy through the chemotherapy control arms of each trial. Baseline characteristics and chemotherapy outcomes in both trials were examined for heterogeneity. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and adverse events (AEs) including immune-related adverse events (irAE) were extracted from trial results. AE results were unavailable for the PD-L1 >/=50% subgroup of KN189, so overall AE results were used. Comparisons were expressed as hazard ratios (HRs) for survival outcomes, and as risk difference (RD) for ORR and toxicity. 507 patients were included: 154 on pembrolizumab, 357 on chemotherapy and 410 on combination. Baseline characteristics of patients in both trials were similar in age, sex, performance status and smoking history. Both trials also had similar chemotherapy outcomes (PFS 6 vs 5 mos) suggesting similar patient prognosis. Network meta-analysis showed no difference between pembrolizumab + chemotherapy and pembrolizumab alone in OS (HR 0.70, 95%CI 0.38-1.30, p=0.26) or PFS (HR 0.72, 95%CI 0.45-1.16, p=0.18), but combination therapy was associated with higher ORR (+21.5%, 95%CI 4.83-38.2%, p=0.011). Overall and grade 3-5 AE rates were higher with combination treatment compared with pembrolizumab alone, but irAE appeared less common with combination treatment (table). Among patients with >/=50% PD-L1 positive NSCLC, pembrolizumab + chemotherapy did not improve OS or PFS compared with pembrolizumab alone, but was associated with higher ORR. Lower rates of irAE with combination therapy are interesting and warrant further study.