Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
Division of Medical Oncology, Cedars-Sinai Cancer, Los Angeles, CA, USA.
Oncologist. 2023 Jul 5;28(7):e498-e507. doi: 10.1093/oncolo/oyad026.
This trial evaluated the safety and efficacy of ipatasertib in combination with carboplatin, carboplatin/paclitaxel, or capecitabine/atezolizumab in patients with metastatic triple-negative breast cancer (mTNBC).
Eligibility criteria were mTNBC, RECIST 1.1 measurable disease, no prior use of platinum for metastatic disease (Arms A and B), and no prior exposure to immune checkpoint inhibitor (Arm C). Primary endpoints were safety and RP2D. Secondary endpoints were progression-free survival (PFS), response rate, and overall survival.
RP2D for Arm A (n = 10) was ipatasertib 300 mg daily, carboplatin AUC2, and paclitaxel 80 mg m-2 days 1, 8, and 15 every 28 days. RP2D for Arm B (n = 12) was ipatasertib 400 mg daily and carboplatin AUC2 days 1, 8, and 15 every 28 days. RP2D for Arm C (n = 6) was likely ipatasertib 300 mg 21 days on 7 days off, capecitabine 750 mg m-2, twice a day, 7 days on 7 days off, and atezolizumab 840 mg days 1 and 15 every 28 days. The most common (≥10%) grade 3-4 AEs at RP2D for Arm A (N = 7 at RP2D) were neutropenia (29%), diarrhea (14%), oral mucositis (14%), and neuropathy (14%); Arm B had diarrhea (17%) and lymphopenia (25%); and Arm C had anemia, fatigue, cognitive disturbance, and maculopapular rash (17% each). Overall responses at RP2D were 29% Arm A, 25% Arm B, and 33% Arm C. PFS was 4.8, 3.9, and 8.2 months for patients on Arms A, B, and C, respectively.
Continuous dosing of ipatasertib with chemotherapy was safe and well-tolerated. Further study is warranted in understanding the role of AKT inhibition in treatment of TNBCs.
NCT03853707.
本试验评估了伊帕替膦联合卡铂、卡铂/紫杉醇或卡培他滨/阿特珠单抗治疗转移性三阴性乳腺癌（mTNBC）患者的安全性和疗效。
入选标准为 mTNBC、RECIST 1.1 可测量疾病、既往无转移性疾病的铂类药物（A 组和 B 组）治疗，且无免疫检查点抑制剂（C 组）暴露。主要终点为安全性和 RP2D。次要终点为无进展生存期（PFS）、反应率和总生存期。
A 组（n=10）的 RP2D 为伊帕替膦 300mg 每日、卡铂 AUC2 和紫杉醇 80mg/m2 第 1、8 和 15 天，每 28 天一次；B 组（n=12）的 RP2D 为伊帕替膦 400mg 每日和卡铂 AUC2 第 1、8 和 15 天，每 28 天一次；C 组（n=6）的 RP2D 可能为伊帕替膦 300mg 21 天，7 天停药，卡培他滨 750mg/m2，每日 2 次，7 天停药，阿特珠单抗 840mg 第 1 和 15 天，每 28 天一次。在 RP2D（n=7）时，A 组最常见（≥10%）的 3-4 级不良事件为中性粒细胞减少（29%）、腹泻（14%）、口腔黏膜炎（14%）和周围神经病变（14%）；B 组为腹泻（17%）和淋巴细胞减少（25%）；C 组为贫血、疲劳、认知障碍和斑丘疹（各 17%）。在 RP2D 时，A 组、B 组和 C 组的总体反应率分别为 29%、25%和 33%。A、B 和 C 组患者的 PFS 分别为 4.8、3.9 和 8.2 个月。
伊帕替膦联合化疗持续给药安全且耐受良好。进一步研究 AKT 抑制在治疗三阴性乳腺癌中的作用是必要的。
NCT03853707。
