Evaluation of pembrolizumab monotherapy in patients with previously treated advanced salivary gland carcinoma in the phase 2 KEYNOTE-158 study.

We evaluated pembrolizumab monotherapy in patients with advanced salivary gland carcinoma on the phase 2 KEYNOTE-158 study (NCT02628067). Eligible patients had histologically/cytologically confirmed advanced salivary gland carcinoma with prior failure or intolerance to standard therapy, measurable disease per Response Evaluation Criteria in Solid Tumours (RECIST) v1.1., and ECOG performance status 0-1. Patients were enrolled irrespective of tumour PD-L1 expression. Patients received pembrolizumab 200 mg Q3W for up to 35 cycles (∼2 years). Radiographic imaging occurred every 9 weeks through month 12, then every 12 weeks. PD-L1 positivity was defined as combined positive score ≥1 (evaluated using PD-L1 IHC 22C3 pharmDx). The primary endpoint was objective response rate per RECIST v1.1. In total, 109 patients were enrolled (PD-L1-positive, 25.7%). At the data cutoff (October 5, 2020), median follow-up was 53.3 (range, 50.8-56.3) months. Objective response rate was 4.6% (95% CI, 1.5-10.4%) among all patients (complete response, n = 1; partial response, n = 4) and was 10.7% (95% CI, 2.3-28.2%) in patients with PD-L1-positive disease and 2.6% (95% CI, 0.3-9.1%) in patients with PD-L1-negative disease. Duration of response was ≥24 months for all 5 responders; median duration of response was not reached (range, 25.1-49.8+ months). Median progression-free survival and overall survival were 4.0 (95% CI, 2.6-4.2) and 21.1 (95% CI, 15.9-25.5) months, respectively. Treatment-related adverse events occurred in 75.2% (grade 3-4, 15.6%; grade 5, 0%) of patients. Immune-mediated adverse events occurred in 22.0% of patients (grade 3, 5.5%; grade 4-5, 0). A small subset of patients with advanced salivary gland carcinoma treated with pembrolizumab had a response; all had response duration ≥2 years. The safety profile of pembrolizumab was manageable.

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Déclaration de conflit d'intérêts

Conflict of interest statement C Even: research support from Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD); participant on advisory boards for Bristol Myers Squibb, MSD, Merck Serono, and Innate Pharma. J-P Delord: funding to the institution for consulting or advisory roles with Novartis, Roche/Genentech, Bristol-Myers Squibb, MSD Oncology, and Pierre Fabre; research funding to the institution from Genentech, Bristol-Myers Squibb, MSD Oncology, AstraZeneca, and Transgene. KA Price: no conflicts to report. K Nakagawa: honoraria from Ono Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., Amgen Inc., Taiyo Pharma Co., Ltd., Nippon Kayaku Co., Ltd., Takeda Pharmaceutical Co., Ltd., AstraZeneca K.K., Life Technologies Japan Ltd., Chugai Pharmaceutical Co., Ltd., Neo Communication, Eli Lilly Japan K.K., Novartis Pharma K.K., MSD K.K., Medical Mobile Communications Co., Ltd, Pfizer Japan Inc., Yodosha Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., CMIC ShiftZero K.K., Taiho Pharmaceutical Co.,Ltd., Japan Clinical Research Operations, Bayer Yakuhin, Ltd., CMIC Co., Ltd.; research funding from IQVIA Services Japan K.K., Eisai Co., Ltd., Syneos Health Clinical K.K., AstraZeneca K.K., EPS Corporation, Mochida Pharmaceutical Co., Ltd., Nippon Kayaku Co.,Ltd., Covance Japan Inc., EPS International Co.,Ltd., Japan Clinical Research Operations, Daiichi Sankyo Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co.,Ltd., GlaxoSmithKline K.K., MSD K.K., Sanofi K.K., Ono Pharmaceutical Co.,Ltd., Chugai Pharmaceutical Co.,Ltd., Amgen Inc., Nippon Boehringer Ingelheim Co., Ltd., Taiho Pharmaceutical Co.,Ltd., SRL, Inc., EP-CRSU Co., Ltd. Medical Research Support, Mebix, Inc., Eli Lilly Japan K.K., Bristol-Myers Squibb K.K., Novartis Pharma K.K., Janssen Pharmaceutical K.K.; Consulting/advisory role with Eli Lilly Japan K.K., Ono Pharmaceutical Co.,Ltd.; patents from Daiichi Sankyo Co., Ltd. D-Y Oh: consultant/advisory board for AstraZeneca, Novartis, Genentech/Roche, Merck Serono, Bayer, Taiho, ASLAN, Halozyme, Zymeworks, BMS/Celgene, BeiGene, Basilea, Turning Point, and Yuhan; research grants from AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, MSD, and Handok. M Burge: honoraria from Merck. HC Chung: funding to the institution from Merck Sharp & Dohme, Lilly, GSK, Merck-Serono, BMS/Ono, Taiho, Amgen, Beigene, Incyte, Zymeworks; advisory boards for Taiho, Celltrion, Merck Sharp & Dohme, Lilly, BMS, Merck-Serono, Gloria, Beigene, Amgen, Zymework; honoraria for lectures from Merck-Serono, Eli Lilly. T Doi: grants from Pfizer, Lilly, Quintiles (IQVIA), Eisai, Merck Serono, Bristol-Myers Squibb, AbbVie, MSD, Daiichi Sankyo, Sumitomo Dainippon, Taiho, Novartis, Janssen, and Boehringer Ingelheim; personal fees from Chugai Pharma, Amgen, Takeda, Bayer, Rakuten Medical, Ono Pharmaceutical, Astellas Pharma, Oncolys BioPharma, Otsuka Pharma, Bristol-Myers Squibb, AbbVie, MSD, Daiichi Sankyo, Sumitomo Dainippon, Taiho, Novartis, Janssen, and Boehringer Ingelheim. M Fakih: consultant to Zhuhai Yufan Biotechnology Co., Ltd., Taiho Oncology, Pfizer Inc, HalioDx, Bayer Corporation, and Mirati Therapeutics, Inc.; advisor to Amgen, Inc., Array BioPharma, Bayer Corporation GlaxoSmithKline, Mirati Therapeutics, Inc., and Seattle Genetics, Inc.; served on speakers’ bureaus for Amgen, Inc. and Guardant360; grants to institution from Amgen, Inc., AstraZeneca Pharmaceuticals, Novartis Oncology, Bristol Myers Squibb, and Verastem. S Takahashi: grants from MSD for the current study; grants and personal fees from Eisai, Novartis, Taiho Pharmaceutical Co., Chugai, Bayer, and Daiichi-Sankyo; grants from AstraZeneca. L Yao: employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. F Jin: employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Owns stock in Merck & Co., Inc. K Norwood: employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Owns stock in Merck & Co., Inc. A Hansen: research funding to the institution from GSK, Merck, Pfizer, MedImmune/Genentech, Roche, Janssen, BMS, AstraZeneca, Astellas, Boehringer Ingelheim, and Bayer; consulting role/advisory boards for GSK, Merck, and Eisai.