Department of Urology and Gynecology, Istituto Nazionale Tumori Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Fondazione G. Pascale, Naples, Italy.
Department of Women and Child Health, Division of Gynecologic Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Gynecol Oncol. 2024 Apr;183:61-67. doi: 10.1016/j.ygyno.2024.02.029. Epub 2024 Mar 21.
Recurrent gynecological tumors (e.g., endometrial, and ovarian cancers) are incurable diseases; therefore, new treatment options are urgently needed. The PTEN-AKT-PI3K pathway is frequently altered in these tumors, representing a potential treatment target. Alpelisib is an α-specific PI3K inhibitor approved in PIK3CA-mutated advanced breast cancer. We report outcomes from a large series of patients with PIK3CA-mutated gynecological cancers prospectively treated with alpelisib within a controlled program.
From April 2021 to December 2022, 36 patients with PIK3CA-mutated advanced gynecological cancers received alpelisib 300 mg orally once daily. Objective response (ORR) and disease control (DCR) rates provided measure of the antitumor activity of alpelisib, the primary objective of the study.
Included patients had endometrial (17/36 [47%]), ovarian (10/36 [28%]), or other gynecological cancers (9/36 [25%]). Most patients had received 2-3 prior systemic treatments (endometrial, 47·2%; ovarian, 60%; other, 56%), and presented with visceral metastases at baseline (82%, 70%, and 56%, respectively). Overall, 17 different PIK3CA mutations were found, including 53% in the kinase domain (most commonly H1047R) and 36% in the helical domain (most commonly E545K). Overall, the ORR was 28% and DCR was 61%, with the greatest benefit observed in patients with endometrial cancer (35% and 71%, respectively).
Alpelisib represents an active treatment option in patients with recurrent gynecological cancers harboring a PIK3CA mutation. These findings support the need of biomarker-driven randomized trials of PI3K inhibitors in gynecological cancers.
复发性妇科肿瘤（如子宫内膜癌和卵巢癌）是无法治愈的疾病；因此，迫切需要新的治疗选择。PTEN-AKT-PI3K 通路在这些肿瘤中经常发生改变，代表了一个潜在的治疗靶点。阿培利司是一种α 特异性 PI3K 抑制剂，已在 PIK3CA 突变的晚期乳腺癌中获得批准。我们报告了在一个受控计划中，对 36 名接受阿培利司治疗的 PIK3CA 突变型妇科癌症患者进行的大型系列前瞻性研究的结果。
从 2021 年 4 月至 2022 年 12 月，36 名 PIK3CA 突变的晚期妇科癌症患者接受了阿培利司 300mg 口服，每日一次。客观缓解率（ORR）和疾病控制率（DCR）是评估阿培利司抗肿瘤活性的指标，也是本研究的主要目的。
入组患者的子宫内膜癌（17/36 [47%]）、卵巢癌（10/36 [28%]）或其他妇科癌症（9/36 [25%]）。大多数患者接受了 2-3 种既往全身治疗（子宫内膜癌，47.2%；卵巢癌，60%；其他，56%），且基线时存在内脏转移（分别为 82%、70%和 56%）。总体上，发现了 17 种不同的 PIK3CA 突变，包括激酶结构域的 53%（最常见的是 H1047R）和螺旋结构域的 36%（最常见的是 E545K）。总体而言，ORR 为 28%，DCR 为 61%，子宫内膜癌患者的获益最大（分别为 35%和 71%）。
阿培利司代表了携带 PIK3CA 突变的复发性妇科癌症患者的一种有效治疗选择。这些发现支持在妇科癌症中进行基于生物标志物的随机 PI3K 抑制剂试验的必要性。
