Dual anti-CTLA-4 and anti-PD-1 blockade in metaplastic carcinoma of the breast: Dart (SWOG S1609, Cohort 36).

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]