Sapanisertib plus exemestane or fulvestrant in women with hormone receptor-positive/HER2-negative advanced or metastatic breast cancer

Bora Lim, David A. Potter, Mohamad A. Salkeni, Paula Silverman, Tufia C. Haddad, Frederic Forget, Ahmad Awada, Jean Luc Canon, Michael Danso, Alain Lortholary, Hugues Bourgeois, Elizabeth Tan-Chiu, Sylvie Vincent, Brittany Bahamon, Kevin J. Galinsky, Chirag Patel, Rachel Neuwirth, E. Jane Leonard, Jennifer R. Diamond

Research output: Contribution to journalArticlepeer-review


Purpose: 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. Patients and Methods: 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). Results: 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). Conclusions: Sapanisertib plus exemestane or fulvestrant was well tolerated and exhibited clinical benefit in postmenopausalwomen with pretreated everolimus-sensitive or everolimus-resistant breast cancer.

Original languageEnglish (US)
Pages (from-to)3329-3338
Number of pages10
JournalClinical Cancer Research
Issue number12
StatePublished - Jun 2021

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Dive into the research topics of 'Sapanisertib plus exemestane or fulvestrant in women with hormone receptor-positive/HER2-negative advanced or metastatic breast cancer'. Together they form a unique fingerprint.

Cite this