Abstract P6-16-03: Phase 2 trial of everolimus and/or trastuzumab in hormone refractory, hormone receptor (HR)-positive, HER2-normal metastatic breast cancer (MBC)

Background: Increased signaling through growth factor pathways including PI3K/Akt/mTOR and HER2 have been implicated in hormone resistance. Everolimus (EVE) improves outcomes when added to endocrine therapy for patients with HR-positive MBC. This study evaluated the efficacy of everolimus (EVE) and trastuzumab (TRAS) in hormone refractory HER2-normal metastatic breast cancer. Methods: Eligible patients had HR-positive, HER2/neu-negative (IHC +1 or +2, HER2-non-amplified) MBC that had progressed within 6 months of the most recent endocrine therapy. Patients continued on the most recent endocrine therapy they received and were randomized to receive EVE 10 mg oral daily or TRAS IV (8 mg/kg loading dose followed by 6 mg/kg every 3 weeks). At progression, the other agent was added (TRAS in the EVE arm and EVE in the TRAS arm). Patients were followed until disease progression or death. Results: 54 eligible patients were included in the analysis, and were randomized to EVE (n=30) or TRAS (n=24). 33% of patients were on fulvestrant, 31% exemestane, 22% tamoxifen and 7% letrozole, which were continued. The median PFS was 5.7 months for EVE vs. 2 months for TRAS until first progression or death with hazard ratio of 0.45 (95% CI 0.25-0.81, p=0.008). Among 48 patients who had disease progression, EVE was added to 16 patients who were originally treated by TRAS, and TRAS was added to 12 patients who were originally treated by EVE; the median time to the second progression was 6.3 months for the arm where EVE was added vs. 3.1 months in the arm where TRAS was added. Three patients were taken off study due to decrease in ejection fraction. Conclusions: This trial demonstrates the efficacy of EVE alone or in combination with TRAS in patients with hormone refractory HR-positive, HER2-negative metastatic breast cancer, who remained on the endocrine therapy they had experienced disease progression on. This suggests that mTOR inhibition has the potential of restoring sensitivity to endocrine therapy and potentially allows the re-use of endocrine agents. Updated results and correlative studies will be presented. Clinical trial information: NCT00912340. Citation Format: Paplomata E, Gogineni K, Meisel J, Santa-Maria C, Yuan L, Kramer J, Bill Li X, Zelnak A, Pakkala S, Kaklamani V, O9Regan R. Phase 2 trial of everolimus and/or trastuzumab in hormone refractory, hormone receptor (HR)-positive, HER2-normal metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-16-03.