Safety and tolerability of pembrolizumab or placebo plus pemetrexed and platinum as first-line therapy in Japanese patients (PTS) with metastatic non-squamous non-small cell lung cancer (NSCLC) enrolled in the phase III KEYNOTE-189 study
Authors: H. Horinouchi, N. Nogami, H. Saka, M. Nishio, T. Tokito, T. Takahashi, K. Kasahara, Y. Hattori, E. Ichihara, N. Adachi, T. Sawada, T. Shimamoto, K. Noguchi, M.C. Pietanza, T. Kurata
Journal: Annals of Oncology (2019)

Background: The global, randomized, double-blind, phase 3 KEYNOTE-189 study (NCT02578680) showed significantly improved OS and PFS with pembrolizumab (pembro) + pemetrexed (pem) + platinum compared with placebo + pem + platinum with a manageable safety profile in pts with previously untreated metastatic nonsquamous NSCLC without targetable EGFR/ALK aberrations|. We present safety and tolerability data from Japanese pts enrolled in KEYNOTE-189. Methods: Eligible pts enrolled in Japan during the global or extension study of KEYNOTE-189 were randomized 2:1 to pembro 200 mg Q3W or placebo for up to 35 cycles (2 y); all pts received pem 500 mg/m2 (until progressive disease or intolerable toxicity) and 4 cycles of carboplatin AUC 5 or cisplatin AUC 75 mg/m2. Safety and tolerability were assessed by clinical review of all relevant parameters; adverse events (AEs) and laboratory abnormalities were graded per NCI CTCAE v4.0. Results: Of 40 pts enrolled in Japan (global study, n = 10; extension study, n = 30), 25 were randomized to the pembro arm, and 15 to the placebo arm. There were no meaningful differences in baseline characteristics, apart from a smaller proportion of pts with brain metastases (16% vs 33%), and larger proportion with PD-L1 TPS <1% (56% vs 40%) and cisplatin recipients (72% vs 53%) in the pembro vs placebo arm, respectively. The median (range) follow-up was 5.6 (2.4–12.9) mo and 7.0 (2.4–19.8) mo in the pembro and placebo arms, respectively. There were no deaths due to AEs. Grade 3/4 AEs occurred in 13 pts (52%) in the pembro arm and 8 (53%) in the placebo arm. 6 (24%) vs 3 pts (20%) had immune-mediated AEs and infusion reactions, with no events of pneumonitis reported in the pembro arm vs 2 (13.3%) in the placebo arm. Overall, AEs led to treatment discontinuation in 4 (16%) pts in the pembro vs 3 (20%) pts in the placebo arm. Conclusions: Pembro + pem + platinum demonstrated a tolerable and manageable safety profile in Japanese pts, generally consistent with the overall pt population in the global KEYNOTE-189 study. No new safety concerns were identified in Japanese pts. Clinical trial identification: NCT02578680. Editorial acknowledgement: Medical writing assistance was provided by Shilpa Aggarwal, PhD, of C4 MedSolutions, LLC (Yardley, PA, USA), a CHC Group company and was funded by funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Legal entity responsible for the study: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Funding: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Disclosure: H. Horinouchi: Corporate-sponsored research: MSD, Eli Lilly, BMS. N. Nogami: Honoraria: Pfizer Inc., Chugai Pharmaceutical Co. Ltd, Eli Lilly, Taiho Pharmaceutical Co. Ltd., AstraZeneca, Kyowa Hakko Kirin, Ono Pharmaceutical Co. Ltd., MSD. H. Saka: Grants/research support: AstraZeneca, MSD, Ono Pharmaceutical; Honoraria: AstraZeneca, MSD, Ono Pharmaceutical, Chugai Pharmaceutical, Boehringer Ingelheim, Kyorin Pharmaceutical. M. Nishio: Grants and personal fees: Ono Pharmaceutical, Bristol-Myers Squibb, Pfizer, Chugai Pharmaceutical, Eli Lilly, Taiho Pharmaceutical, AstraZeneca, Boehringer-Ingelheim, MSD, Novartis; Personal fees: Daiichi Sankyo Healthcare, Merck Serono; Grants: Astellas, outside the submitted work. T. Tokito: Honoraria: AstraZeneca, MSD, Ono, Chugai. T. Takahashi: Grants, personal fees: Ono Pharmaceutical Co., Ltd., MSD K.K., AstraZeneca KK, Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K.; Grants: Pfizer Japan Inc.; Personal fees: Boehringer Ingelheim Japan, Inc, Roche Diagnostics K.K. K. Kasahara: Grants, honoraria: Boehringer Ingelheim; Honoraria: Pfizer, Chugai Pharmaceutical, Eli Lilly, Taiho Pharmaceuticals, AstraZeneca, MSD. Y. Hattori: Research funding: MSD, Ono; Honoraria: AstraZeneca, Boehringer Ingelheim, Chugai, Eli Lilly, MSD, Novartis, Ono, Taiho. E. Ichihara: Research grants: Eli Lilly, MSD. N. Adachi, T. Sawada, T. Shimamoto, K. Noguchi: Employee: MSD K.K., Tokyo, Japan. M.C. Pietanza: Employee: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. T. Kurata: Research grants: AstraZeneca, MSD; Honoraria: AstraZeneca, MSD, Ono, Bristol-Myers Squibb, Chugai, Eli Lilly.