{"id":347,"title":"Olaparib plus tremelimumab in women with recurrent ovarian cancer and a germline BRCA1 or BRCA2 mutation: a phase I/II study","title_zh":"奥拉帕利联合曲美木单抗治疗复发性卵巢癌胚系BRCA1/2突变女性的I/II期研究","url":"https://pubmed.ncbi.nlm.nih.gov/42982866","doi":"10.1038/s41467-026-78395-y","pmid":"42982866","journal":"Nat Commun","kind":"paper","lang":"en","published_at":"2026-10-08T00:00:00+00:00","fetched_at":"2026-11-08T03:44:12+00:00","authors":["Adams SF","Gimotty PA","Rutledge TL","O'Malley DM","Ring K","Wenham RM","Finkelstein K","Lokich E","Falcon DM","Yeckes A","Oyebamiji OM","Brayer KJ","Paskus E","Falk NK","Richards R","Lee JH","Eberhardt SC","McCance D","Paliard X","Boyle S","Chen R","Kang H","Conejo-Garcia JR","Rixe O","Muller CY"],"primary_topic":"oocyte","topics":[{"slug":"oocyte","score":4.0,"hits":["ovarian"]},{"slug":"ivg-stem","score":4.0,"hits":["germline"]}],"topic_score":4.0,"preference_score":0.0,"preference_labels":[],"llm_score":52.0,"final_score":60.0,"score_dims":{"novelty":60,"rigor":70,"impact":45,"relevance":20,"translation":30},"recommend_reason":"研究设计规范、来自高影响力期刊，但主题为卵巢癌肿瘤免疫联合治疗，与生殖医学/辅助生殖核心实践距离较远，仅对关注胚系BRCA相关生殖遗传咨询者有一定参考价值。","keywords":["卵巢癌","BRCA1/2","PARP抑制剂","CTLA4抑制剂","胚系突变"],"selected":1,"story_id":418,"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":"nat-commun","journal_tier":"cns-sub","journal_if":14.7,"is_mock":false,"summary_zh":"该多中心单臂I/II期研究纳入50例携带胚系BRCA1或BRCA2突变的复发性上皮性卵巢癌女性，评估PARP抑制剂奥拉帕利联合CTLA4免疫检查点抑制剂曲美木单抗的安全性与疗效。I期未见新毒性；联合安全队列中57%发生3/4级非血液学毒性，34.7%停用曲美木单抗。II期主要终点客观缓解率为32.7%，疾病控制率47.7%，中位无进展生存3.0个月，总生存24.3个月。探索性分析提示VSTM5或IFIT1B低表达与治疗获益及PFS改善相关，结论需生物标志物筛选获益人群。","summary":"Response rates to immune checkpoint blockade (ICB) in ovarian cancer are low. In preclinical studies, poly(ADP-ribose) polymerase inhibition (PARPi) synergized with CTLA4 ICB to achieve long-term survival in Brca1-deficient ovarian cancer models. Here we evaluated the safety and efficacy of combined treatment with the PARPi olaparib and the CTLA4 ICB tremelimumab for recurrent epithelial ovarian cancer in a multi-site single-arm phase I/II study enrolling 50 women with germline BRCA1 or BRCA2 mutations (NCT02571725). In phase I, no new toxicities were identified (n = 3). In the combined phase I and II safety cohort (n = 49), 57% of subjects experienced grade 3 or 4 non-hematologic toxicity, with tremelimumab discontinuation in 34.7%. The primary phase II endpoint, overall response rate was 32.7% (95% CI 19.5-45.8%), and disease control rate was 47.7% (95% CI 33.0-62.5%). Secondary outcomes were progression-free survival (PFS, 3.0 months, 95% CI 2.7-5.9), and overall survival (24.3 months, CI 14.9-30.4). In exploratory post-hoc biomarker analyses, low VSTM5 or IFIT1B expression was associated with treatment benefit and improved PFS (p 12 months in 6 subjects among this heavily pre-treated cohort highlight the need for biomarkers to select regimens for patients with recurrent ovarian cancer.","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}}