Pembrolizumab After Two or More Lines of Previous Therapy in Patients With Recurrent or Metastatic SCLC: Results From the KEYNOTE-028 and KEYNOTE-158 Studies

doi:10.1016/j.jtho.2019.12.109

Journal of Thoracic Oncology

Volume 15, Issue 4, April 2020, Pages 618-627

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Abstract

Introduction

Pembrolizumab has shown clinical benefit in patients with previously treated recurrent or metastatic SCLC in the phase 1b multicohort study KEYNOTE-028 (NCT02054806) and the phase 2 multicohort study KEYNOTE-158 (NCT02628067). We present a pooled analysis of patients from KEYNOTE-028 and KEYNOTE-158 who had received two or more lines of previous therapy for SCLC.

Methods

Eligible patients were aged 18 years and above, had histologically or cytologically confirmed incurable recurrent or metastatic SCLC, had an Eastern Cooperative Oncology Group performance status of 1 and below, and had received two or more lines of previous therapy. Patients in KEYNOTE-028 were required to have a programmed death ligand 1 (PD-L1)–positive tumor. Patients received pembrolizumab (10 mg/kg every 2 weeks in KEYNOTE-028 or 200 mg every 3 weeks in KEYNOTE-158) for up to 2 years. The primary end point was objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1, which is presented here per independent review.

Results

Eighty-three patients who had received two or more lines of previous therapy (KEYNOTE-028, n = 19; KEYNOTE-158, n = 64) were included. Median follow-up duration was 7.7 (range, 0.5–48.7) months. Objective response rate was 19.3% (95% confidence interval: 11.4–29.4); two patients had complete response (one with a PD-L1–positive tumor), and 14 patients had partial response (13 with PD-L1–positive tumors). The median duration of response was not reached (range, 4.1‒35.8+ mo; plus sign indicates ongoing response); 61% of responders had responses lasting 18 months or longer. Fifty-one patients (61.4%) experienced any-grade treatment-related adverse events; eight patients (9.6%) had grade 3 or higher events.

Conclusions

Pembrolizumab exhibited durable antitumor activity in a subset of patients with recurrent or metastatic SCLC who had undergone two or more previous lines of therapy, regardless of PD-L1 expression. Pembrolizumab was well tolerated.

Keywords

Third-line therapy

Pembrolizumab

SCLC

Immunotherapy

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: Disclosure: Dr. Chung received grant and research support from Eli Lilly, GlaxoSmithKline, Merck Sharp and Dohme Corp., Merck-Serono, Bristol-Myers Squibb/Ono Pharmaceutical, and Taiho; received honoraria from Merck-Serono, Eli Lilly/Foundation Medicine; and consulted Taiho, Celltrion, Merck Sharp and Dohme Corp., Eli Lilly, Quintiles, Bristol-Myers Squibb, and Merck-Serono. Dr. Piha-Paul received research/grant funding (through her institution) from AbbVie Inc., Alkermes, Aminex Therapeutics, Amphivena Therapeutics Inc., BioMarin Pharmaceutical Inc, Boehringer Ingelheim, Bristol-Myers Squibb, Cerulean Pharma Inc., Chugai Pharmaceutical Co., Ltd, Curis Inc., Daiichi Sankyo, Eli Lilly, Five Prime Therapeutics, Genmab A/S, GlaxoSmithKline, Helix BioPharma Corp., Incyte Corp., Jacobio Pharmaceuticals Co., Ltd., Medimmune, LLC, Medivation Inc., Merck Sharp and Dohme Corp., NewLink Genetics Corporation/Blue Link Pharmaceuticals, Novartis Pharmaceuticals, Pieris Pharmaceuticals Inc., Pfizer, Principia Biopharma Inc., Puma Biotechnology Inc., Rapt Therapeutics Inc., Seattle Genetics, Taiho Oncology, Tesaro Inc., TransThera Bio, and XuanZhu Biopharma; and is the recipient of an NCI/NIH Core Grant (P30CA016672 – CCSG shared resources). Dr. Lopez-Martin reports grants, personal fees, nonfinancial support, and other from PharmaMar, Bristol-Myers Squibb, Merck Sharp and Dohme Corp., and Roche; reports grants, personal fees, and other from Novartis; reports grants and other from AstraZeneca during the conduct of the study; reports personal fees from Pierre Fabre, Amgen, Chobani, Lilly, and Celgene, outside the submitted work; is a former employee of PharmaMar. Dr. Schellens received personal payments from Modra Pharmaceuticals and Debiopharm, is a shareholder in Modra Pharmaceuticals, and is a patent-holder on oral taxanes. Dr. Kao received honoraria paid to his institution by Roche, Merck Sharp and Dohme Corp., Bristol-Myers Squibb, AstraZeneca, and Boehringer Ingelheim and received travel funds from Roche, Bristol-Myers Squibb, AstraZeneca, and Boehringer Ingelheim. Dr. Miller served as a consultant in the advisory board for Bristol-Myers Squibb, Merck, Roche, Novartis, Amgen, and GlaxoSmithKline; received institutional research grants from Bristol-Myers Squibb, Pfizer, Amgen, Roche, MedImmune, Merck, Novartis, AstraZeneca, and Methylgene; and served as a speaker and received honoraria from Bristol-Myers Squibb, Merck, Roche, Novartis, and GlaxoSmithKline. Dr. Delord received grants and research support from Bristol-Myers Squibb, Genentech, Novartis, MSD, and AstraZeneca and received honoraria for occasional consultancy from Merck Sharp and Dohme Corp., Roche, Bristol-Myers Squibb, AstraZeneca, and Amgen. Dr. Gao has received a grant from Pfizer and is a consultant for Merck. Dr. Planchard has provided consulting/advisory services or lectures for AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, MedImmune, Novartis, Pfizer, prIME Oncology, Peer CME, and Roche; received honoraria from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, and Roche; performed clinical trials research as principal and coinvestigator (institutional financial interests) for AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, MedImmune, Sanofi-Aventis, Taiho Pharma, Novocure, and Daiichi Sankyo; and received travel and accommodation expenses from AstraZeneca, Roche, Novartis, prIME Oncology, and Pfizer. Dr. Zer received research grants from Bristol-Myers Squibb and received consultant fees, honoraria, and travel grants from Roche, Bristol-Myers Squibb, Merck Sharp and Dohme Corp., Boehringer Ingelheim, AstraZeneca, and Takeda. Dr. Jalal received research funding from AstraZeneca, Tesaro, and Astex. Dr. Mehnert served as a consultant and advisor for Genentech, EMD Serono, Merck Sharp and Dohme Corp., Amgen, and Boehringer Ingelheim and received institution research funding from Merck Sharp and Dohme Corp., Polynoma, Immunocore, Amgen, AstraZeneca, Incyte, and Macrogenics. Dr. Bennouna served in the advisory boards for Roche, Boehringer Ingelheim, Merck Sharp and Dohme Corp., Bristol-Myers Squibb, AstraZeneca, and Servier; received institutional grants from AstraZeneca; and organized symposiums for Roche, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, and Servier. Dr. Kim has received institutional research funding from Alpha Biopharma, AstraZeneca/MedImmune, Hanmi, Janssen, Merus, Mirati Therapeutics, Merck Sharp and Dohme Corp., Novartis, Ono Pharmaceutical, Pfizer, Roche/Genentech, Takeda, TP Therapeutics, Xcovery, and Yuhan. Drs. Xu, Krishnan, and Norwood are employees of Merck Sharp and Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey, USA. Dr. Ott received grants and research support paid to the institution from Merck, Bristol-Myers Squibb, Roche/Genentech, NeonTherapeutics, ArmoBiosciences, Celldex, AstraZeneca/MedImmune, Novartis, and Pfizer and received consulting fees from Merck, Bristol-Myers Squibb, Roche/Genentech, NeonTherapeutics, Celldex, AstraZeneca/MedImmune, Novartis, Pfizer, Array, and Amgen. The remaining authors declare no conflict of interest.