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

Miyako Satouchi, Kaname Nosaki, Toshiaki Takahashi, Kazuhiko Nakagawa, Keisuke Aoe, Takayasu Kurata, Akimasa Sekine, Atsushi Horiike, Tatsuro Fukuhara, Shunichi Sugawara, Shigeki Umemura, Hideo Saka, Isamu Okamoto, Nobuyuki Yamamoto, Hiroshi Sakai, Kazuma Kishi, Nobuyuki Katakami, Hidehito Horinouchi, Toyoaki Hida, Hiroaki Okamoto, Shinji Atagi, Tatsuo Ohira, Shi Rong Han, Kazuo Noguchi, Victoria Ebiana, Katsuyuki Hotta, Miyako Satouchi, Kaname Nosaki, Toshiaki Takahashi, Kazuhiko Nakagawa, Keisuke Aoe, Takayasu Kurata, Akimasa Sekine, Atsushi Horiike, Tatsuro Fukuhara, Shunichi Sugawara, Shigeki Umemura, Hideo Saka, Isamu Okamoto, Nobuyuki Yamamoto, Hiroshi Sakai, Kazuma Kishi, Nobuyuki Katakami, Hidehito Horinouchi, Toyoaki Hida, Hiroaki Okamoto, Shinji Atagi, Tatsuo Ohira, Shi Rong Han, Kazuo Noguchi, Victoria Ebiana, Katsuyuki Hotta

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 higher 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). Median progression-free survival was 41.4 (95% confidence interval [CI], 4.2-42.5) months with pembrolizumab and 4.1 (95% CI, 2.8-8.3) months with chemotherapy (hazard ratio [HR], 0.27 [95% CI, 0.11-0.65]; one-sided, nominal P = .001). Median overall survival was not reached (NR) (95% CI, 22.9-NR) and 21.5 (95% CI, 5.2-35.0) months, respectively (HR, 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 pembrolizumab-treated patients (52%) and four chemotherapy-treated 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 higher. The trial is registered with Clinicaltrials.gov: NCT02142738.

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

Conflict of interest statement

Miyako Satouchi has received honoraria from MSD, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol‐Myers Squibb, AstraZeneca, Taiho Pharmaceutical, Pfizer, Novartis, Eli Lilly, and Boehringer Ingelheim and grants from MSD, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol‐Myers Squibb, AstraZeneca, Pfizer, Novartis, Boehringer Ingelheim, AbbVie, Takeda, and Eli Lilly. Toshiaki Takahashi has received research funds from AstraZeneca, Chugai Pharmaceutical, Eli Lilly Japan, Ono Pharmaceutical, MSD, Tokyo, and Pfizer Japan. Kazuhiko Nakagawa has received lecture fees, honoraria, or other fees from AstraZeneca, Astellas Pharma, MSD, Tokyo, Ono Pharmaceutical, Nippon Boehringer Ingelheim, Eli Lilly Japan, Pfizer Japan, and Kyorin Pharmaceutical, research funds from MSD, Tokyo, A2 Healthcare, inVentiv Health Japan, Astellas Pharma, Daiichi Sankyo, Eisai, AbbVie, IQVIA Services Japan, ICON Japan, Chugai Pharmaceutical, Takeda Pharmaceutical, Nippon Boehringer Ingelheim, Syneos Health, Pfizer Japan, Eli Lilly Japan, SymBio Pharmaceuticals, Bristol‐Myers Squibb, CMIC Shift Zero, Taiho Pharmaceutical, Kyowa Hakko Kirin, Ono Pharmaceutical, and AstraZeneca and scholarship endowments or research grants from Takeda Pharmaceutical, Ono Pharmaceutical, Bristol‐Myers Squibb, Nippon Boehringer Ingelheim, Daiichi Sankyo, and Chugai Pharmaceutical. Keisuke Aoe has received lecture fees, honoraria, or other fees from Ono and Bristol‐Myers Squibb and research funds from Ono, Bristol‐Myers Squibb, MSD, AstraZeneca, Novartis, and Eli Lilly. Takayasu Kurata has received lecture fees, honoraria, or other fees from MSD, Ono, Bristol‐Myers Squibb, AstraZeneca, Chugai, Eli Lilly, and Boehringer Ingelheim and research funds from MSD, AstraZeneca, Takeda, Bristol‐Myers Squibb, and Novartis. Tatsuro Fukuhara has received research funds from MSD, Ono Pharma, Bristol‐Myers Squibb, and AstraZeneca. Shunichi Sugawara has received lecture fees from MSD. Shigeki Umemura has received research funds from MSD. Hideo Saka has received research funds from MSD, AstraZeneca, Ono, Parexel International, WJOG, Bristol‐Myers Squibb, Chugai, and Takeda. Isamu Okamoto has received lecture fees, honoraria, or other fees from MSD, Eli Lilly, Chugai, Ono, and AstraZeneca and research funds from MSD, Eli Lilly, Chugai, Ono, and AstraZeneca. Nobuyuki Yamamoto has received lecture fees, honoraria, or other fees from MSD, AstraZeneca, Ono Pharmaceutical, Eli Lilly, Boehringer Ingelheim, Novartis, and Pfizer and research funds from Bristol‐Myers Squibb, Amgen, MSD, Astellas, AstraZeneca, Ono Pharmaceutical, Daiichi Sankyo, Taiho Pharmaceutical, Takeda Pharmaceutical, Chugai Pharmaceutical, Terumo, Toppan Printing, Eli Lilly, Boehringer Ingelheim, Novartis, and Pfizer. Kazuma Kishi has received research funds from MSD. Nobuyuki Katakami obtained speakers fees and research grants from AstraZeneca, Taiho, Boehringer Ingelheim Japan, MSD, and Chugai Pharma. Hidehito Horinouchi has received lecture fees, honoraria, or other fees from Eli Lilly, AstraZeneca, Kyowa Kirin, MSD, Ono, and Bristol‐Myers Squibb and research funds from Chugail, Daiichi Sankyo, AstraZeneca, MSD, Ono, Bristol‐Myers Squibb, and Genomic Health. Toyoaki Hida has received research funds from MSD, Bristol‐Myers Squibb, and Ono. Hiroaki Okamoto has received research funds from Taiho, Chugai, Astellas, Eli Lilly, Merck, and Bristol‐Myers Squibb. Shinji Atagi has received research funds from AstraZeneca, MSD, Eli Lilly, Chugai, Ono, Taiho, Boehringer Ingelheim, Pfizer, F. Hoffman‐La Roche, and Bristol‐Myers Squibb. Shi Rong Han and Kazuo Noguchi are employees of MSD, Tokyo, Japan. Victoria Ebiana is a former employee of Merck Sharp & Dohme, a subsidiary of Merck & Co., Inc, Kenilworth, NJ, USA, and has received remuneration from MSD and Amgen. Katsuyuki Hotta has received lecture fees, honoraria, or other fees from MSD and AstraZeneca and research funds from AstraZeneca, Chugai, Eli Lilly, Bristol‐Myers Squibb, and Astellas. The other authors have no conflict of interest.

© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Figures

FIGURE 1
FIGURE 1
CONSORT flow diagram of Japanese patients enrolled in KEYNOTE‐024 to evaluate pembrolizumab vs chemotherapy in metastatic non‐small‐cell lung cancer. 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
FIGURE 2
Kaplan‐Meier estimates of (A) progression‐free survival per RECIST version 1.1 per independent central review and (B) overall survival in patients with metastatic non‐small‐cell lung cancer treated with pembrolizumab or chemotherapy. CI, confidence interval; HR, hazard ratio; NR, not reached; RECIST, response evaluation criteria in solid tumors
FIGURE 3
FIGURE 3
Duration of treatment and time to response among patients in the pembrolizumab arm of KEYNOTE‐024 with a complete response (CR) or partial response (PR) per RECIST version 1.1 by independent central review. Bar lengths indicate duration of treatment (first‐course, dark green; second‐course, medium green) and months of follow‐up (light green). Tumor response (ie, CR, PR, SD, PD) is expressed per RECIST version 1.1 by independent central review only. AE, adverse event; PD, progressive disease; PD‐L1, programmed death ligand 1; SD, stable disease; TPS, tumor proportion score

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