Randomized clinical trial of pembrolizumab vs chemotherapy for previously untreated Chinese patients with PD-L1-positive locally advanced or metastatic non-small-cell lung cancer: KEYNOTE-042 China Study

Abstract

In the global KEYNOTE-042 study (Clinicaltrials.gov, NCT02220894), pembrolizumab significantly improved overall survival (OS) vs chemotherapy in patients with previously untreated programmed death ligand 1 (PD-L1)-positive locally advanced/metastatic non-small-cell lung cancer (NSCLC) without EGFR/ALK alterations. We present results from patients in KEYNOTE-042 enrolled from China in the global or extension study (NCT03850444; protocol identical to global study). Patients were randomized 1:1 (stratified by ECOG performance status 0 vs 1, squamous vs nonsquamous histology and PD-L1 tumor proportion score [TPS] ≥50% vs 1%-49%) to 35 cycles of pembrolizumab 200 mg every 3 weeks (Q3W) or investigator's choice of 4 to 6 cycles of carboplatin plus paclitaxel or pemetrexed Q3W with optional pemetrexed maintenance for nonsquamous tumors. Primary endpoints were OS in patients with PD-L1 TPS ≥50%, ≥20% or ≥1%. Two hundred sixty-two patients (pembrolizumab, n = 128; chemotherapy, n = 134) were enrolled from China. At data cutoff (February 21, 2020; median follow-up, 33.0 [range, 25.6-41.9] months), pembrolizumab was shown to improve OS vs chemotherapy in patients with PD-L1 TPS ≥50% (hazard ratio [95% CI], 0.63 [0.43-0.94]), TPS ≥20% (0.66 [0.47-0.92]) and TPS ≥1% (0.67 [0.50-0.89]). Grade 3 to 5 treatment-related adverse events occurred less frequently with pembrolizumab vs chemotherapy (19.5% vs 68.8%). In 22 patients who completed 35 cycles of pembrolizumab, objective response rate was 77.3% and median duration of response was 27.6 months. Consistent with the global KEYNOTE-042 study, pembrolizumab improved OS vs chemotherapy in this study of Chinese patients with locally advanced/metastatic NSCLC and PD-L1 TPS ≥1%, supporting first-line pembrolizumab monotherapy for PD-L1-positive advanced/metastatic NSCLC in China.

Keywords: chemotherapy; non-small-cell lung cancer; pembrolizumab; programmed death ligand 1.

FIGURE 1

Overall survival (OS) analyses in the intention‐to‐treat population. Kaplan‐Meier estimates of OS among patients with (A) PD‐L1 TPS ≥50%; (B) PD‐L1 TPS ≥20%; and (C) PD‐L1 TPS ≥1%. (D) PD‐L1 TPS 1%‐49%; (E) OS analysis in key subgroups in patients with PD‐L1 TPS ≥1%. Vertical dotted line in subgroup analysis represents HR in the overall population. The intention‐to‐treat population comprised all patients who were randomized to treatment, according to the treatment assigned. OS was defined as time from randomization to death from any cause. ECOG PS, Eastern Cooperative Oncology Group performance status; HR, hazard ratio; NR, not reached; PD‐L1, programmed death ligand 1; TPS, tumor proportion score [Color figure can be viewed at wileyonlinelibrary.com]