Pembrolizumab plus pemetrexed-platinum for metastatic nonsquamous non-small-cell lung cancer: KEYNOTE-189 Japan Study

Abstract

Pembrolizumab plus pemetrexed-platinum significantly improved overall survival (OS) and progression-free survival (PFS) with manageable safety compared with placebo plus pemetrexed-platinum in patients with previously untreated metastatic nonsquamous non-small-cell lung cancer (NSCLC) without EGFR/ALK alterations in the global, randomized, double-blind, phase 3 KEYNOTE-189 study. We present results of Japanese patients enrolled in the KEYNOTE-189 global and Japan extension studies. Patients were randomized 2:1 to intravenous pembrolizumab 200 mg or placebo every 3 weeks (Q3W) for up to 35 cycles. All patients received pemetrexed 500 mg/m² plus the investigator's choice of cisplatin or carboplatin Q3W for four cycles, followed by maintenance pemetrexed 500 mg/m² Q3W (all intravenous). Co-primary endpoints were OS and PFS. Forty Japanese patients enrolled (pembrolizumab, n = 25; placebo, n = 15). At data cutoff (20 May 2019; median time from randomization to data cutoff, 18.5 [range, 14.7-38.2] months), the median OS was not reached in the pembrolizumab plus pemetrexed-platinum arm; the median OS was 25.9 (95% confidence interval [CI], 11.9-29.0) months in the placebo plus pemetrexed-platinum arm (hazard ratio [HR] .29; 95% CI, .07-1.15). The median (95% CI) PFS was 16.5 (8.8-21.1) compared with 7.1 (4.7-21.4) months (HR, .62; 95% CI, .27-1.42), respectively. There were no grade 5 adverse events (AE). Grade 3/4 AE occurred in 72% vs 60% of patients in the pembrolizumab vs placebo arms; 40% vs 20% had immune-mediated AE, and 4% vs 0% had infusion reactions. Efficacy and safety outcomes were similar to those from the global study and support first-line therapy with pembrolizumab plus pemetrexed-platinum in Japanese patients with nonsquamous NSCLC without EGFR/ALK alterations.

Keywords: Japan; PD-L1 protein; non-small-cell lung carcinoma; pembrolizumab; treatment outcome.

FIGURE 1

Disposition of patients in the study. PD‐1, programmed death 1; PD‐L1, programmed death ligand 1. ^aIncludes patients with clinical progression or progressive disease. ^bIncludes patients who received subsequent antineoplastic therapy. It excludes 1 patient in the pembrolizumab combination arm who received radiation (see Table S1 for further details)

FIGURE 2

Kaplan‐Meier analysis of (A) OS and (B) PFS in the intent‐to‐treat population. HR, hazard ratio; NR, not reached; OS, overall survival; PFS, progression‐free survival

FIGURE 3

Treatment duration and time to response among patients in the pembrolizumab plus pemetrexed‐platinum group. Light green bars indicate the months of follow up. AE, adverse event; CR, complete response; PD, progressive disease; PR, partial response

FIGURE 4

Kaplan‐Meier analysis of progression‐free survival‐2 (PFS2) in the intent‐to‐treat population. PFS2 was defined as the time from randomization to objective tumor progression on next‐line treatment (including subsequent anti–PD‐[L]1 therapy) or death from any cause, whichever occurred first. HR, hazard ratio; NR, not reached; PD‐(L)1, programmed death 1 or programmed death ligand 1