Dual anti-CTLA-4 and anti-PD-1 blockade in metaplastic carcinoma of the breast: Dart (SWOG S1609, Cohort 36).
Sylvia Adams, Megan Othus, Sandip Pravin Patel, Young Kwang Chae, Kathy D. Miller, Rashmi Chugh, Scott M. Schuetze, Elad Sharon, Larissa A. Korde, Robert J. Gray, Edward Mayerson, Melissa Plets, Razelle Kurzrock
Abstract
1073 Background: Immune checkpoint blockade, specifically anti-CTLA-4 and anti-PD-1-directed approaches, has improved outcomes in various tumors and is being tested in SWOG S1609 in rare solid tumors (DART=Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors). Metaplastic breast cancer (MpBC) is a rare subtype of breast cancer with poor response to cytotoxics and median survival of < 1 year for metastatic disease. A MpBC stratum was added based on promising activity of immunotherapy in a patient with MpBC (Adams, npj Breast Cancer 2017). Here, we report the MpBC cohort of S1609 DART. Methods: In this prospective, open-label, multicenter phase II trial patients received ipilimumab (1mg/kg q6 weeks) plus nivolumab (240mg intravenously every 2 weeks). Eligibility for cohort 36 required histologically confirmed MpBC, measurable disease, and ECOG PS 0-2. Prior anti-CTLA4 or anti-PD-1/PD-L1 treatment (but not both) was permitted as well as treated brain metastases. The primary endpoint was overall response rate (ORR, confirmed CR, PR) by RECIST v1.1; 2 or more responses in 16 patients was considered a success. Secondary endpoints: toxicity (CTCAE v4.0), PFS and ORR by immune-related RECIST (iRECIST), overall survival (OS). Biomarker analyses are ongoing. Results: Nineteen patients were registered to the cohort and seventeen eligible patients received therapy. The median age was 60 (range 26-85), most tumors were high grade, triple negative and had a high ki67 (median 87%), median prior therapy = 2 lines. The ORR was 12% (RECIST 1.1) and 18% (iRECIST), with ongoing responses at 23, 18 and 11 months, respectively; SD was seen in 24%, none > 6 months (Table). Median OS was 12 months. AEs were observed in 11 patients (65%), with 3 patients (18%) having Grade 3/4 AEs and 1 patient with a fatal AE (myocarditis). The most common toxicities were LFT abnormalities and fatigue. Conclusions: Cohort 36 met its primary endpoint: ipilimumab plus nivolumab was clinically active in advanced MpBC, with durable responses observed in 3/17 patients. Further investigation of this combination is warranted. Clinical trial information: NCT02834013 . [Table: see text]