Phase II Study Combining Pembrolizumab with Aromatase Inhibitor in Patients with Metastatic Hormone Receptor Positive Breast Cancer

SIMPLE SUMMARY: Aromatase inhibitors (AIs) remain key elements of endocrine therapy for patients with hormone receptor positive HER2 negative metastatic breast cancer (HR(+) HER2(−) MBC). Recent advances include the use of CDK 4/6 inhibitors or PIK3CA inhibitor in the clinic; however, few immunotherapy trials have been conducted in HR(+) HER2(−) metastatic disease. The current phase II trial was designed to test the safety and efficacy of AIs in combination with immune checkpoint inhibitor pembrolizumab in patients with HR(+) HER2(−) MBC (NCT 02648477). This combination was well tolerated, but minimal clinical activity was observed likely due to lack of PD-L1 pre-selection and heavily pretreated patient population. ABSTRACT: This study investigated the safety and antitumor activity of aromatase inhibitors (AI) with immune checkpoint inhibitor (ICI) pembrolizumab in patients with hormone receptor positive (HR(+)) human epidermal growth factor receptor 2-negative (HER2(−)) metastatic breast cancer (MBC) in a phase II study with a safety lead-in (NCT 02648477). Patients received pembrolizumab plus AI up to 2 years or until confirmed progression or unacceptable toxicity. Key eligibility criteria were HR(+) HER2(−) MBC; RECIST v1.1 measurable disease; adequate organ function; and ECOG 0-1. Primary endpoints were safety and overall response rate. A 3-at-risk design was used for the safety lead-in with a targeted accrual of 20 patients. Grade 2 adverse events (AEs) included 35% fatigue, 20% rash, and 10% hot flashes. Grade 3 immune-related AEs (irAEs) related to pembrolizumab included 5% elevated AST/ALT, 5% rash, and 5% lymphopenia. Two (10%) patients had partial responses, three (15%) had stable disease, and 15 (75%) had progression of disease. Median progression-free survival was 1.8 months (95% CI 1.6, 2.6), median overall survival was 17.2 months (95% CI 9.4, NA), and median follow-up time was 40.1 months (range 31.3–46.8 months). The combination was well tolerated, but clinical activity was comparable to AI alone.