依西美坦
富维斯特朗
医学
依维莫司
内科学
转移性乳腺癌
肿瘤科
雌激素受体
芳香化酶抑制剂
不利影响
临床研究阶段
乳腺癌
皮疹
粘膜炎
癌症
芳香化酶
临床试验
化疗
作者
Bora Lim,David A. Potter,Mohamad A. Salkeni,Paula Silverman,Tufia C. Haddad,Fréd́eric Forget,Ahmad Awada,Jean Luc Canon,Michael Danso,Alain Lortholary,Hugues Bourgeois,Elizabeth Tan-Chiu,Sylvie Vincent,Brittany Bahamón,Kevin Galinsky,Chirag Patel,Rachel Neuwirth,E. Jane Leonard,Jennifer R. Diamond
标识
DOI:10.1158/1078-0432.ccr-20-4131
摘要
This open-label, multicenter, phase IB/II study evaluated sapanisertib, a dual inhibitor of mTOR kinase complexes 1/2, plus exemestane or fulvestrant in postmenopausal women with hormone receptor-positive (HR+)/HER2-negative (HER2-) advanced/metastatic breast cancer.Eligible patients had previously progressed on everolimus with exemestane/fulvestrant and received ≤3 (phase IB) or ≤1 (phase II) prior chemotherapy regimens. Patients received sapanisertib 3 to 5 mg every day (phase IB), or 4 mg every day (phase II) with exemestane 25 mg every day or fulvestrant 500 mg monthly in 28-day cycles. Phase II enrolled parallel cohorts based on prior response to everolimus. The primary objective of phase II was to evaluate antitumor activity by clinical benefit rate at 16 weeks (CBR-16).Overall, 118 patients enrolled in phase IB (n = 24) and II (n = 94). Five patients in phase IB experienced dose-limiting toxicities, at sapanisertib doses of 5 mg every day (n = 4) and 4 mg every day (n = 1); sapanisertib 4 mg every day was the MTD in combination with exemestane or fulvestrant. In phase II, in everolimus-sensitive versus everolimus-resistant cohorts, CBR-16 was 45% versus 23%, and overall response rate was 8% versus 2%, respectively. The most common adverse events were nausea (52%), fatigue (47%), diarrhea (37%), and hyperglycemia (33%); rash occurred in 17% of patients. Molecular analysis suggested positive association between AKT1 mutation status and best treatment response (complete + partial response; P = 0.0262).Sapanisertib plus exemestane or fulvestrant was well tolerated and exhibited clinical benefit in postmenopausal women with pretreated everolimus-sensitive or everolimus-resistant breast cancer.
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