{"id":376,"title":"First-line pembrolizumab versus carboplatin plus paclitaxel in participants with mismatch repair-deficient advanced or recurrent endometrial cancer (KEYNOTE-C93/GOG-3064/ENGOT-en15): interim analysis of a multicentre, open-label, randomised, active-comparator controlled, phase 3 trial","title_zh":"一线帕博利珠单抗对比卡铂联合紫杉醇治疗错配修复缺陷晚期或复发性子宫内膜癌：KEYNOTE-C93/GOG-3064/ENGOT-en15 III期试验中期分析","url":"https://pubmed.ncbi.nlm.nih.gov/42933458","doi":"10.1016/s0140-6736(26)02095-7","pmid":"42933458","journal":"Lancet","kind":"paper","lang":"en","published_at":"2026-10-26T00:00:00+00:00","fetched_at":"2026-11-08T03:44:12+00:00","authors":["Slomovitz BM","Zhu J","Yin R","Backes F","Bidziński M","Gilbert L","Willmott LJ","Hasegawa K","Kim JW","Kroep JR","Romero I","Gultekin M","Wang PH","Baron-Hay S","Klát J","Rosengarten O","Polignano M","Berrios M","Cadoo K","Lassus H","Maćkowiak-Matejczyk B","Lorusso D","Reyners AKL","Burton ER","Makker V","Yao L","Meng R","Orlowski R","Pignata S"],"primary_topic":"endometrium","topics":[{"slug":"endometrium","score":4.0,"hits":["endometrial"]},{"slug":"repro-immunology","score":1.0,"hits":["immunotherapy"]}],"topic_score":4.0,"preference_score":0.0,"preference_labels":[],"llm_score":74.0,"final_score":80.0,"score_dims":{"novelty":78,"rigor":95,"impact":72,"relevance":35,"translation":55},"recommend_reason":"Lancet III期随机对照证据级别高，为dMMR子宫内膜癌一线去化疗提供了重要数据；但属肿瘤治疗研究，与ART、胚胎实验室的直接相关性有限，生殖领域读者可按兴趣浏览。","keywords":["子宫内膜癌","错配修复缺陷","帕博利珠单抗","免疫治疗","III期临床试验","无进展生存期"],"selected":1,"story_id":318,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-top-journals","source_name":"PubMed · CNS/大子刊/四大医学刊（生殖相关）","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":"lancet","journal_tier":"general-top","journal_if":98.4,"is_mock":false,"summary_zh":"该多中心开放标签III期试验纳入299例不可手术III/IV期、持续、晚期或复发dMMR子宫内膜癌患者，1:1随机接受一线帕博利珠单抗或卡铂+紫杉醇。中期分析显示，帕博利珠单抗组中位PFS为38.2个月，化疗组为8.4个月（HR 0.57，p=0.0002）；OS未达预设显著性；≥3级治疗相关不良事件发生率分别为18%与51%。提示一线免疫单药可显著改善PFS并降低毒性，但未与免疫+化疗标准方案直接比较。","summary":"BACKGROUND: A need exists for first-line chemotherapy-free options in advanced or recurrent endometrial cancer. We therefore assessed the efficacy, quality of life, and safety of first-line pembrolizumab versus carboplatin plus paclitaxel in mismatch repair-deficient (dMMR) advanced or recurrent endometrial cancer. METHODS: The KEYNOTE-C93/GOG-3064/ENGOT-en15 multicentre, open-label, randomised, active-comparator controlled, phase 3 trial was conducted at 122 centres in 24 countries in the Americas, Asia, Europe, and Oceania. Adult participants (≥18 years) with inoperable, stage III or IV, persistent, advanced, or recurrent dMMR endometrial cancer were randomly assigned 1:1 to intravenous pembrolizumab 400 mg every 6 weeks for up to 18 cycles or intravenous carboplatin area under the curve 5 mg/mL or 6 mg/mL per min plus paclitaxel 175 mg/m2 on day 1 of each 3-week cycle for six cycles. Randomisation was stratified by disease status, histology, and previous receipt of (neo)adjuvant chemotherapy. Primary endpoints were progression-free survival per RECIST version 1.1, by blinded independent central review, and overall survival. This trial is registered at ClinicalTrials.gov, NCT05173987, and is ongoing. FINDINGS: Between Feb 22, 2022, and Dec 12, 2023, 299 participants were assigned to pembrolizumab (n=149) or carboplatin plus paclitaxel (n=150). At the cutoff for the prespecified interim analysis in the intention-to-treat population (April 24, 2026), median progression-free survival was 38·2 months (95% CI 17·9 months-not reached) in the pembrolizumab group versus 8·4 months (6·8-10·4) in the carboplatin plus paclitaxel group (hazard ratio [HR] 0·57, 95% CI 0·42-0·79; p=0·0002). Estimated progression-free survival was 75% (95% CI 67-81) versus 76% (68-82) at 6 months, 67% (59-74) versus 40% (32-48) at 12 months, and 53% (44-61) versus 30% (22-38) at 36 months. The prespecified statistical significance criterion for overall survival was not met at the interim analysis (medians not reached; HR 0·77, 95% CI 0·52-1·15; p=0·10). Grade 3 or higher treatment-related adverse events occurred in 27 (18%) of 149 participants in the pembrolizumab group and 73 (51%) of 144 in the carboplatin plus paclitaxel group. Treatment-related adverse events of any grade that occurred in at least 25% of participants in either group included alopecia (three [2%] of 149 in the pembrolizumab group, 72 [50%] of 144 in the carboplatin plus paclitaxel group), anaemia (seven [5%], 71 [49%]), nausea (seven [5%], 41 [28%]), decreased neutrophil count (five [3%], 40 [28%]), peripheral neuropathy (none, 38 [26%]), and fatigue (20 [13%], 37 [26%]). Treatment-related adverse events led to treatment discontinuation in 14 (9%) of 149 participants in the pembrolizumab group and 21 (15%) of 144 participants in the carboplatin plus paclitaxel group; they resulted in death in two participants in the pembrolizumab group (hepatic failure and bacterial meningitis [n=1 each]) and one participant in the carboplatin plus paclitaxel group (pulmonary embolism). INTERPRETATION: First-line pembrolizumab showed a statistically significant and clinically meaningful improvement in progression-free survival, with lower frequency of overall and grade 3 or above treatment-related adverse events. The study did not compare pembrolizumab monotherapy with the current standard of care (immunotherapy plus chemotherapy). FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co.","interpretation_basis":null,"fulltext_status":null,"interpretation":null,"fulltext":{"available":false,"status":null,"reason":"尚未抓取全文（未入选、分数未达阈值，或还没跑 fulltext 步骤）","pmcid":null,"license":null,"chars":0,"source":null,"fetched_at":null}}