TY - JOUR
T1 - Pembrolizumab plus pemetrexed-platinum for metastatic nonsquamous non–small-cell lung cancer
T2 - KEYNOTE-189 Japan Study
AU - Horinouchi, Hidehito
AU - Nogami, Naoyuki
AU - Saka, Hideo
AU - Nishio, Makoto
AU - Tokito, Takaaki
AU - Takahashi, Toshiaki
AU - Kasahara, Kazuo
AU - Hattori, Yoshihiro
AU - Ichihara, Eiki
AU - Adachi, Noriaki
AU - Noguchi, Kazuo
AU - Souza, Fabricio
AU - Kurata, Takayasu
N1 - Funding Information:
Hidehito Horinouchi: Lecture fees, honoraria, or other fees from Eli Lilly, AstraZeneca, Kyowa Kirin, MSD, Ono Pharmaceutical, and Bristol‐Myers Squibb; Research funds from Chugai Pharmaceutical, Daiichi Sankyo, AstraZeneca, MSD, Ono Pharmaceutical, Bristol‐Myers Squibb, and Genomic Health. Naoyuki Nogami: Honoraria from AstraZeneca, Chugai Pharmaceutical, Pfizer Japan Inc, Eli Lilly Japan KK, Ono Pharmaceutical, Taiho Pharmaceutical, MSD KK, Kyowa Kirin, Bristol‐Myers Squibb KK, and Nippon Boehringer Ingelheim. Hideo Saka: Nothing to disclose. Makoto Nishio: Honoraria for lectures and consulting from Ono Pharmaceutical, Bristol‐Myers Squibb, Pfizer, Chugai Pharmaceutical, Eli Lilly, Taiho Pharmaceutical, AstraZeneca, Boehringer Ingelheim, MSD, and Novartis; Research support from MSD, Novartis, Ono Pharmaceutical, Chugai Pharmaceutical, Bristol‐Myers Squibb, Taiho Pharmaceutical, Eli Lilly, AstraZeneca, and Pfizer. Takaaki Tokito: Personal fees from AstraZeneca, Chugai Pharmaceutical, MSD, and Boehringer Ingelheim. Toshiaki Takahashi: Grants and personal fees from AstraZeneca KK, Chugai Pharmaceutical, Eli Lilly Japan KK, Ono Pharmaceutical, and MSD KK; Grants from Pfizer Japan Inc; Personal fees from Boehringer Ingelheim Japan, Inc and Roche Diagnostics KK. Kazuo Kasahara: Grants from Boehringer Ingelheim. Yoshihiro Hattori: Lecture fees from Taiho Pharmaceutical; Grants from Ono Pharmaceutical and MSD. Eiki Ichihara: Honoraria from Boehringer Ingelheim; Research support from MSD. Noriaki Adachi: Employee of MSD KK. Kazuo Noguchi: Employee of MSD KK. Fabricio Souza: Employee of Merck & Co., Inc. Takayasu Kurata: Personal fees from AstraZeneca, MSD, Eli Lilly, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol‐Myers Squibb, Boehringer Ingelheim, and Pfizer; Grants from AstraZeneca, MSD, Chugai Pharmaceutical, Takeda, and Bristol‐Myers Squibb.
Funding Information:
Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Medical writing assistance was provided by Adrienne Drinkwater, PhD, and Shilpa Kamboj, PhD, of ICON plc (North Wales, PA, USA). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. A portion of the results from this study were presented at the 60th Annual Meeting of the Japan Lung Cancer Society; 6−8 December 2019; Osaka, Japan.
Publisher Copyright:
© 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
PY - 2021/8
Y1 - 2021/8
N2 - 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.
AB - 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.
KW - Japan
KW - PD-L1 protein
KW - non–small-cell lung carcinoma
KW - pembrolizumab
KW - treatment outcome
UR - http://www.scopus.com/inward/record.url?scp=85108008840&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85108008840&partnerID=8YFLogxK
U2 - 10.1111/cas.14980
DO - 10.1111/cas.14980
M3 - Article
C2 - 34036692
AN - SCOPUS:85108008840
VL - 112
SP - 3255
EP - 3265
JO - Cancer Science
JF - Cancer Science
SN - 1347-9032
IS - 8
ER -