Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO) and Centre Léon Bérard, University Claude Bernard, Lyon, France.
GINECO and Institut Jean Godinot, Reims, France.
Nat Commun. 2024 Jul 16;15(1):5931. doi: 10.1038/s41467-024-46999-x.
This open-label, non-comparative, 2:1 randomized, phase II trial (NCT03275506) in women with stage IIIC/IV high-grade serous carcinoma (HGSC) for whom upfront complete resection was unachievable assessed whether adding pembrolizumab (200 mg every 3 weeks) to standard-of-care carboplatin plus paclitaxel yielded a complete resection rate (CRR) of at least 50%. Postoperatively patients continued assigned treatment for a maximum of 2 years. Postoperative bevacizumab was optional. The primary endpoint was independently assessed CRR at interval debulking surgery. Secondary endpoints were Completeness of Cytoreduction Index (CCI) and peritoneal cancer index (PCI) scores, objective and best response rates, progression-free survival, overall survival, safety, postoperative morbidity, and pathological complete response. The CRR in 61 pembrolizumab-treated patients was 74% (one-sided 95% CI = 63%), exceeding the prespecified ≥50% threshold and meeting the primary objective. The CRR without pembrolizumab was 70% (one-sided 95% CI = 54%). In the remaining patients CCI scores were ≥3 in 27% of the standard-of-care group and 18% of the investigational group and CC1 in 3% of the investigational group. PCI score decreased by a mean of 9.6 in the standard-of-care group and 10.2 in the investigational group. Objective response rates were 60% and 72%, respectively, and best overall response rates were 83% and 90%, respectively. Progression-free survival was similar with the two regimens (median 20.8 versus 19.4 months in the standard-of-care versus investigational arms, respectively) but overall survival favored pembrolizumab-containing therapy (median 35.3 versus 49.8 months, respectively). The most common grade ≥3 adverse events with pembrolizumab-containing therapy were anemia during neoadjuvant therapy and infection/fever postoperatively. Pembrolizumab was discontinued prematurely because of adverse events in 23% of pembrolizumab-treated patients. Combining pembrolizumab with neoadjuvant chemotherapy is feasible for HGSC considered not completely resectable; observed activity in some subgroups justifies further evaluation to improve understanding of the role of immunotherapy in HGSC.
这项开放标签、非对照、2:1 随机、二期临床试验（NCT03275506）纳入了无法进行初始完全切除的 IIIC/IV 期高级别浆液性卵巢癌（HGSC）女性患者，评估了在标准护理卡铂加紫杉醇的基础上加用 pembrolizumab（每 3 周 200mg）能否使完全切除率（CRR）至少达到 50%。术后患者继续接受最多 2 年的指定治疗。术后 bevacizumab 为可选。主要终点为间隔性肿瘤细胞减灭术时独立评估的 CRR。次要终点包括细胞减灭术完全程度指数（CCI）和腹膜肿瘤指数（PCI）评分、客观缓解率和最佳缓解率、无进展生存期、总生存期、安全性、术后发病率和病理完全缓解。61 名接受 pembrolizumab 治疗的患者的 CRR 为 74%（单侧 95%CI=63%），超过了预设的≥50%的阈值，达到了主要目标。未接受 pembrolizumab 治疗的患者的 CRR 为 70%（单侧 95%CI=54%）。在其余患者中，标准护理组的 CCI 评分≥3 的比例为 27%，研究组为 18%，CC1 为 3%。标准护理组 PCI 评分平均下降 9.6，研究组下降 10.2。客观缓解率分别为 60%和 72%，最佳总缓解率分别为 83%和 90%。两种方案的无进展生存期相似（标准护理组中位 20.8 个月，研究组中位 19.4 个月），但总生存期有利于含 pembrolizumab 的治疗（中位 35.3 个月 vs. 49.8 个月）。含 pembrolizumab 治疗最常见的≥3 级不良事件为新辅助治疗期间贫血和术后感染/发热。由于不良事件，23%的 pembrolizumab 治疗患者提前停止了 pembrolizumab 的治疗。在考虑不完全可切除的 HGSC 中，将 pembrolizumab 联合新辅助化疗是可行的；在某些亚组中观察到的活性证实了进一步评估的合理性，以提高对免疫疗法在 HGSC 中的作用的理解。
