Pembrolizumab for previously treated advanced anal squamous cell carcinoma: results from the non-randomised, multicohort, multicentre, phase 2 KEYNOTE-158 study
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Background: Outcomes in advanced anal squamous cell carcinoma are poor, with few treatment options and controlled clinical trials. We evaluated the efficacy and safety of pembrolizumab in patients with advanced anal squamous cell carcinoma (cohort A) from the phase 2 KEYNOTE-158 study. Methods: Eligible patients enrolled in the ongoing non-randomised, multicohort, multicentre, phase 2 KEYNOTE-158 study, which was done across 38 centres worldwide, were aged 18 years or older; had histologically or cytologically confirmed advanced or metastatic anal squamous cell carcinoma; had previous failure of or intolerance to standard therapy or no standard therapy options; and had a PD-L1-evaluable tissue sample. Patients received pembrolizumab 200 mg intravenously every 3 weeks for 2 years, or until disease progression, unacceptable toxicity, investigator's decision to withdraw the patient from the study, or withdrawal of patient consent. The primary endpoint was objective response, as assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Efficacy and safety analyses included all patients who received at least one dose of pembrolizumab. The trial is registered with ClinicalTrials.gov, NCT02628067. Findings: Between March 3, 2016, and July 23, 2018, 163 patients were screened, of whom 112 were enrolled and treated in the anal cancer cohort. 91 (81%) patients were female, 104 (93%) had M1 disease, and 75 (67%) had PD-L1-positive tumours. The median time from first dose to data cutoff (June 27, 2019) was 34·7 months (IQR 32·5–36·4). 12 (11%, 95% CI 6–18) patients had an objective response, including 11 (15%, 8–25) of 75 patients with PD-L1-positive tumours and one (3%; 0–17) of 30 patients with PD-L1-negative tumours. 68 (61%) patients had treatment-related adverse events (20 [18%] patients had grade 3–4 adverse events), the most common of which were fatigue (17 patients), diarrhoea (13), hypothyroidism (13), and nausea (13). Serious treatment-related adverse events occurred in 12 (11%) patients. 25 (22%) patients had immune-mediated adverse events, and one (1%) had an infusion reaction. There were no treatment-related deaths. Interpretation: Pembrolizumab monotherapy is a possible treatment option with a favourable benefit–risk ratio for patients with previously treated advanced anal squamous cell carcinoma who have no alternative satisfactory treatment options. Funding: Merck Sharp & Dohme.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | The Lancet Gastroenterology and Hepatology |
| Vol/bind | 7 |
| Udgave nummer | 5 |
| Sider (fra-til) | 446-454 |
| Antal sider | 9 |
| ISSN | 2468-1253 |
| DOI | |
| Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:
AM received institutional research funding from Merck Sharp & Dohme (MSD) ; a grant from Fondation MSD Avenir outside the topic of the manuscript; and honoraria and travel expenses for participation in a scientific advisory board from MSD outside the topic of the submitted work. PAC received financial support (paid to their institution) for conduct of clinical study from MSD, AbbVie, Amgen, Bayer, Bristol Myers Squibb, Merck Serono, Novartis, Roche/Genentech, GlaxoSmithKline, Janssen, Lilly, AstraZeneca, Celgene, Taiho, Toray, Transgene, Loxo, and Innate Pharma; grants from MSD and Novartis; personal fees from Blueprint (for advisory board), Amgen, Merck Serono, Novartis, and Roche/Genentech; non-financial support from MSD, Novartis, AstraZeneca, and Plexxikon; and travel and accommodations from MSD, Novartis, Roche/Genentech, and Netris Pharma. MF received honoraria from Amgen; personal fees for an advisory role for Amgen, Array BioPharma, Bayer, and BGB Group/GlaxoSmithKline; personal fees for speaker bureau participation for Amgen and Guardant360; and personal fees for consulting for Pfizer, Bayer, Taiho Oncology, Seattle Genetics, Zhuhai Biotech, and Incyte. SK received research funding (paid to their institution) from MSD; personal fees (paid to their institution) from Bristol Myers Squibb, Pfizer, Roche, AstraZeneca, Takeda, Boehringer Ingelheim, and Specialised Therapeutics; and grants to institution from AstraZeneca. AI reports grants from MSD, Merck, Bayer, Roche, AstraZeneca, and Bristol Myers Squibb; personal fees from Bayer, Roche, and Springworks; and non-financial support from Seven and Eight. MGJV received institutional research funding from MSD. GMB received research funding from mAbxience, MSD, and Bristol Myers Squibb. PAA received research funding from Bristol Myers Squibb, Roche-Genentech, Array, and Sanofi; received personal fees for advisory and consultancy roles for Bristol Myers Squibb, Roche-Genentech, MSD, Array, Novartis, Merck Serono, Pierre Fabre, Incyte, MedImmune, AstraZeneca, Syndax, Sun Pharma, Sanofi, Idera, Ultimovacs, Sandoz, Immunocore, 4SC, Alkermes, Nektar, Italfarmaco, Boehringer-Ingelheim, Eisai, Regeneron, Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore, and Seagen; received personal fees for travel support from MSD; and served as an unpaid consultant for Takis. AS is on the advisory board for Bristol Myers Squibb, Servier, Gilead, Pfizer, Eisai, Bayer, and MSD; does consultancy for Arqule and Sanofi; and is on the speaker's bureau for Takeda, Bristol Myers Squibb, Roche, AbbVie, Amgen, Celgene, Servier, Gilead, AstraZeneca, Pfizer, Arqule, Eli Lilly, Sandoz, Eisai, Novartis, Bayer, and MSD. MS received research grants from MSD and Eli Lilly. ST received grants from MSD, Eisai, Novartis, Taiho, AstraZeneca, Chugai, Bayer, and Daiichi-Sankyo; and personal fees from Eisai, Novartis, Taiho, Chugai, Bayer, and Daiichi-Sankyo. SAP-P received clinical trial research support (paid to their institution) from AbbVie, ABM Therapeutics, Acepodia, Alkermes, Aminex Therapeutics, Amphivena Therapeutics, Bristol Myers Squibb, Cerulean Pharma, Chugai Pharmaceutical, Curis, Daiichi Sankyo, Eli Lilly, ENB Therapeutics, Five Prime Therapeutics, F-Star Therapeutics, Gene Quantum, Genmab, GlaxoSmithKline, Helix BioPharma Corp, Incyte Corp, Jacobio Pharmaceuticals, MedImmune, Medivation, MSD, Novartis Pharmaceuticals, Pieris Pharmaceuticals, Pfizer, Principia Biopharma, Puma Biotechnology, Rapt Therapeutics, Seattle Genetics, Silverback Therapeutics, Taiho Oncology, Tesaro, TransThera Bio, NCI/NIH P30CA016672–Core Grant (CCSG Shared Resources), Cyclacel Pharmaceuticals, F-Star Beta, HiberCell, and Synologic; and received clinical trial research support from BioMarin Pharmaceutical and Boehringer Ingelheim. PAO received grants from Bristol Myers Squibb, Genentech, Celldex, Cytomx, Pfizer, Neon Therapeutics, Armo Biosciences, and AstraZeneca; and personal fees from Bristol Myers Squibb, Genentech, Celldex, Cytomx, Pfizer, Alexion, Amgen, Novartis, Neon Therapeutics, and Array. AC, FJ, and KN are employees of MSD, and have stock ownership in Merck & Co. All other authors declare no competing interests.
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© 2022 Elsevier Ltd
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