帕博利珠单抗联合奥拉帕利治疗铂类化疗后进展的复发性宫颈癌：GOTIC-025 II期研究
这项多中心、研究者发起的单臂II期试验纳入28例既往接受过铂类化疗、未用过免疫检查点抑制剂的复发性宫颈癌患者，给予帕博利珠单抗（200 mg 每3周）联合奥拉帕利（600 mg 每日）治疗。安全性总体可控，但≥3级不良事件发生率为60.7%。
要点
- ORR仅3.8%，提示在PD-1阻断基础上加PARP抑制剂在该小样本中活性有限。
- DCR达50.0%，中位PFS为3.4个月，重度经治人群仍可见一定疾病控制。
- 安全性总体可控，但≥3级不良事件60.7%，以血液学毒性最常见。
核心结论
- 帕博利珠单抗联合奥拉帕利治疗铂类化疗后进展的复发性宫颈癌安全性可控，但抗肿瘤活性有限。
研究设计与样本
- 多中心、研究者发起的单臂II期试验（GOTIC-025），纳入28例既往接受铂类化疗、未用过免疫检查点抑制剂的复发性宫颈癌患者。
- 治疗方案为帕博利珠单抗200 mg 每3周联合奥拉帕利600 mg 每日，直至疾病进展或出现不可接受的毒性。
- 主要终点为客观缓解率（ORR），次要终点为无进展生存期（PFS）、总生存期（OS）和安全性。
主要发现
- 无患者因不良事件停用帕博利珠单抗，4例因不良事件停用奥拉帕利；全部患者出现不良事件，≥3级事件占60.7%，血液学毒性最常见。
临床怎么用
- 该联合方案在重度经治的复发性宫颈癌中活性有限，不宜作为常规推荐，需结合患者既往治疗线数个体化评估。
- 治疗期间应重点监测血液学毒性，奥拉帕利相关不良事件可导致停药。
局限性
- 单臂、小样本设计，未设对照，结果需谨慎解读。
- ORR的置信区间较宽，疗效估计不确定性大。
以上解读依据论文摘要（全文未开放获取或许可不允许翻译转载）。
原文
OBJECTIVE: Treatment options for recurrent cervical cancer, particularly after platinum-based chemotherapy and immunotherapy, remain limited. However, PD-1 blockade is effective in patients naïve to immune checkpoint inhibitors. Further, PARP inhibition may modulate the tumor immune microenvironment and enhance the efficacy of PD-1 blockade therapy. This study evaluated the efficacy and safety of pembrolizumab plus olaparib for cervical cancer. METHODS: This multi-center, investigator-initiated, single-arm phase II trial enrolled immunotherapy-naive patients with recurrent cervical cancer who previously received platinum-based chemotherapy. Patients received pembrolizumab (200 mg every three weeks) and olaparib (600 mg daily) until disease progression or unacceptable toxicity. The primary outcome was objective response rate (ORR), and secondary outcomes were progression-free survival (PFS), overall survival (OS) and safety. RESULTS: Among enrolled 28 patients, 14 had squamous cell carcinoma, 20 received ≥2 prior chemotherapy regimens. Twenty-two patients had prior bevacizumab. Twenty-six patients were evaluable for response. The ORR was 3.8% (90% CI, 0.2%-17.0%); the disease control rate was 50.0%. The median PFS was 3.4 months. No patients required discontinuation of pembrolizumab; 4 patients discontinued olaparib due to adverse events (AEs). All patients experienced AEs with grade ≥ 3 events in 60.7%, and hematologic toxicities were the most common severe events. CONCLUSIONS: We investigated the combination of pembrolizumab and olaparib in patients with platinum-treated recurrent cervical cancer and demonstrated manageable safety. However, adding a PARP inhibitor to PD-1 blockade showed limited activity in this small cohort. Although the ORR was modest, DCR and median OS were numerically encouraging in this heavily pretreated population.
引用
- Ogasawara A, Suzuki S, Oda K, et al. Phase II study of pembrolizumab plus olaparib in recurrent cervical cancer progressing after platinum-based chemotherapy (GOTIC-025). Gynecol Oncol. 2026. PMID: 42013608. doi:10.1016/j.ygyno.2026.04.007
供执业医师工作参考，不替代临床判断；数值与分级以指南原文为准。