{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T22:58:53Z","timestamp":1792277933726,"version":"4.4.0"},"reference-count":36,"publisher":"American Medical Association (AMA)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Oncol"],"published-print":{"date-parts":[[2025,4,1]]},"abstract":"Importance<\/jats:title>Advanced clear cell gynecological cancers (CCGCs) have a poor prognosis, with response rates to second-line chemotherapy less than 8%. Preliminary clinical activity with programmed cell death 1 protein (PD-1) inhibitors reported in CCGC merits further investigation.<\/jats:p><\/jats:sec>Objective<\/jats:title>To assess the clinical benefit of pembrolizumab in patients with previously treated advanced CCGC.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>The PEACOCC trial is a single-arm multicenter phase 2 trial conducted at 5 UK centers investigating the clinical benefit and safety of pembrolizumab. PD-1 inhibitor\u2013naive patients with histologically confirmed advanced CCGC, radiological disease progression following 1 or more prior courses of chemotherapy, and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 to 1 were included. Patients were enrolled from March 2019 to October 2021, with data collected until July 2024.<\/jats:p><\/jats:sec>Interventions<\/jats:title>Pembrolizumab, 200 mg, intravenously every 21 days up to 2 years until progression, discontinuation due to toxic effects, or patient\/clinician decision. Up to 1 year of retreatment on diseases progression, if stable disease, partial response, or complete response at 2 years.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>The primary end point was progression-free survival (PFS) rate at 12 weeks using Response Evaluation Criteria in Solid Tumors version 1.1 to detect a 12-week PFS rate of 33% or greater and exclude a PFS rate of less than 15%, with 90% power and 1-sided 5% significance level. Secondary end points included objective response rate, duration of response, PFS, overall survival, safety, and quality of life.<\/jats:p><\/jats:sec>Results<\/jats:title>A total of 48 patients were eligible. The median (range) age was 58.5 (32-77) years, and 26 (54%) had an ECOG PS score of 0 and 22 (46%) had an ECOG PS score of 1; 41 (85%) had ovarian, 6 (13%) had endometrial, and 1 (2%) had cervical advanced CCGC. The median (range) courses prior therapy was 3 (1-6); 19 patients (40%) received prior anti-angiogenic therapy, and 19 (40%) had a platinum-free interval of more than 12 months. Grade 3 treatment-related adverse events were observed in 9 patients (19%), and no patients had grade 4 or 5 adverse events. A total of 45 of 46 patients (98%) had mismatch repair\u2013proficient tumors. The 12-week PFS rate was 42% (95% CI, 28-57), and the best objective response rate was 25% (95% CI, 14-40), with 12 partial responses. After a median follow-up of 46.9 months (95% CI, 43.4-55.0), the median PFS was 2.7 months (95% CI, 1.3-5.4), and the median overall survival was 14.8 months (95% CI, 6.7-28.2).<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>The PEACOCC trial showed clinical benefit with pembrolizumab in patients with previously treated advanced CCGC, of whom all except 1 had MMR-proficient disease. Clinical outcomes were durable with an overall tolerable safety profile, justifying further evaluation of pembrolizumab monotherapy for advanced CCGC in a randomized clinical trial.<\/jats:p><\/jats:sec>Trial Registration<\/jats:title>ClinicalTrials.gov Identifier: NCT03425565<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1001\/jamaoncol.2024.6797","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T16:32:15Z","timestamp":1738859535000},"page":"377","source":"Crossref","is-referenced-by-count":43,"title":["Pembrolizumab in Patients With Advanced Clear Cell Gynecological Cancer"],"prefix":"10.1001","volume":"11","author":[{"given":"Rebecca","family":"Kristeleit","sequence":"first","affiliation":[{"name":"Guy\u2019s and St Thomas\u2019 NHS Foundation Trust and Comprehensive Cancer Centre, King\u2019s College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael-John","family":"Devlin","sequence":"additional","affiliation":[{"name":"Queen Mary University of London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Clamp","sequence":"additional","affiliation":[{"name":"The Christie NHS Foundation Trust and University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlie","family":"Gourley","sequence":"additional","affiliation":[{"name":"Edinburgh Cancer Centre, Western General Hospital, Edinburgh, United Kingdom"},{"name":"Nicola Murray Centre for Ovarian Cancer Research, Cancer Research United Kingdom Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"Roux","sequence":"additional","affiliation":[{"name":"Oxford University Hospitals NHS Foundation Trust, Churchill Hospital, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcia","family":"Hall","sequence":"additional","affiliation":[{"name":"Hillingdon Hospitals NHS Foundation Trust, Mount Vernon Hospital, Middlesex, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Nirsimloo","sequence":"additional","affiliation":[{"name":"Edinburgh Cancer Centre, Western General Hospital, Edinburgh, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentinos","family":"Kounnis","sequence":"additional","affiliation":[{"name":"Oxford University Hospitals NHS Foundation Trust, Churchill Hospital, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesley","family":"Sage","sequence":"additional","affiliation":[{"name":"Gynae-Oncology Trials Group United Kingdom and Ovacome, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priya","family":"Narayanan","sequence":"additional","affiliation":[{"name":"University College London Hospitals, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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