First-line pembrolizumab vs chemotherapy in metastatic non-small-cell lung cancer: KEYNOTE-024 Japan subset

Abstract

This prespecified subanalysis of the global, randomized controlled phase III KEYNOTE-024 study of pembrolizumab vs chemotherapy in previously untreated metastatic non-small-cell lung cancer without EGFR/ALK alterations and a programmed death-ligand 1 (PD-L1) tumor proportion score of 50% or greater evaluated clinical outcomes among patients enrolled in Japan. Treatment consisted of pembrolizumab 200 mg every 3 weeks (35 cycles) or platinum-based chemotherapy (four to six cycles). The primary end-point was progression-free survival; secondary end-points included overall survival and safety. Of 305 patients randomized in KEYNOTE-024 overall, 40 patients were enrolled in Japan (all received treatment: pembrolizumab, n = 21; chemotherapy, n = 19). The hazard ratio (HR) for progression-free survival by independent central review (data cut-off date, 10 July 2017) was 0.25 (95% confidence interval [CI], 0.10-0.64; one-sided, nominal P = .001). The HR for overall survival (data cut-off date, 15 February 2019) was 0.39 (95% CI, 0.17-0.91; one-sided, nominal P = .012). Treatment-related adverse events occurred in 21/21 (100%) pembrolizumab-treated and 18/19 (95%) chemotherapy-treated patients; eight patients (38%) and nine patients (47%), respectively, had grade 3-5 events. Immune-mediated adverse events and infusion reactions occurred in 11 patients (52%) and four patients (21%), respectively; four patients (19%) and one patient (5%), respectively, had grade 3-5 events. Consistent with results from KEYNOTE-024 overall, first-line pembrolizumab improved progression-free survival and overall survival vs chemotherapy with manageable safety among Japanese patients with metastatic non-small-cell lung cancer without EGFR/ALK alterations and a PD-L1 tumor proportion score of 50% or greater. The trial is registered with ClinicalTrials.gov: NCT02142738.

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

FIGURE 1

CONSORT flow diagram of recruitment of the Japan subset of patients with previously untreated metastatic non‐small‐cell lung cancer in the KEYNOTE‐024 study of pembrolizumab vs chemotherapy. ^aThe remaining patients did not meet study eligibility criteria (n = 14). ^bIncludes 10 patients who crossed over to pembrolizumab treatment during the study. ^cIncludes clinical progression. PD‐L1, programmed death‐ligand 1; TPS, tumor proportion score

FIGURE 2

Kaplan‐Meier estimates of (A) progression‐free survival (PFS) per RECIST version 1.1 per independent central review (data cut‐off date, 10 July 2017), (B) PFS per RECIST version 1.1 per investigator review (data cut‐off date, 15 February 2019), and (C) overall survival (OS) in the subset of patients with previously untreated metastatic non‐small‐cell lung cancer in the KEYNOTE‐024 study of pembrolizumab vs chemotherapy. CI, confidence interval; HR, hazard ratio; NR, not reached.

FIGURE 3

Duration of treatment and time to response among patients in the pembrolizumab arm of the KEYNOTE‐024 study with an objective response (ie, complete response or partial response [PR]) per RECIST version 1.1 by investigator review (data cut‐off, date 15 February 2019). Bar lengths indicate duration of treatment (first course, dark green; second course, medium green) and months of follow‐up (light green). Tumor response (ie, PR, stable disease [SD], and progressive disease [PD]) is expressed per RECIST version 1.1 by investigator review only. AE, adverse event; PD–L1, programmed death‐ligand 1; TPS, tumor proportion score