Data from A Multicenter Phase II Trial of Ipilimumab and Nivolumab in Unresectable or Metastatic Metaplastic Breast Cancer: Cohort 36 of Dual Anti–CTLA-4 and Anti–PD-1 Blockade in Rare Tumors (DART, SWOG S1609)
Year: 2023
Type: other
Abstract: Purpose: Metaplastic breast cancer (MpBC) is a rare aggressive subtype that responds poorly to cytotoxics. Median survival is approximately 8 months for metastatic disease. We report results for advanced MpBC treated with ipilimumab + nivolumab, a cohort of S1609 for rare cancers (DART: NCT02834013). Patients and Methods: Prospective, open-label, multicenter phase II (two-stage) trial of ipilimumab (1 mg/kg i.v. every 6 weeks) plus nivolumab (240 mg i.v. every 2 weeks) for advanced MpBC. Primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and toxicity. Results: Overall, 17 evaluable patients enrolled. Median age was 60 years (26–85); median number of prior therapy lines was 2 (0–5). ORR was 18%; 3 of 17 patients achieved objective responses (1 complete, 2 partial responses; 2 spindle cell, 1 chondromyxoid histology), which are ongoing at 28+, 33+, and 34+ months, respectively. Median PFS and OS were 2 and 12 months, respectively. Altogether, 11 patients (65%) experienced adverse events (AE), including one grade 5 AE. Eight patients (47%) developed an immune-related AE (irAE), with adrenal insufficiency observed in all 3 responders. Responses occurred in tumors with low tumor mutational burden, low PD-L1, and absent tumor-infiltrating lymphocytes. Conclusions: The ipilimumab and nivolumab combination showed no new safety signals and met its primary endpoint with 18% ORR in advanced, chemotherapy-refractory MpBC. All responses are ongoing at >2 to almost 3 years later. The effect of ipilimumab and nivolumab was associated with exceptional responses in a subset of patients versus no activity. This combination warrants further investigation in MpBC, with special attention to understanding mechanism of action, and carefully designed to weigh against the significant risks of irAEs.
Authors: Sylvia Adams, Megan Othus, Sandip Pravin Patel, Kathy D. Miller, Rashmi Chugh, Scott M. Schuetze, Mary D. Chamberlin, Barbara J. Haley, Anna Maria V. Storniolo, Mridula P. Reddy, Scott A. Anderson, Collin T. Zimmerman, Anne P. O'Dea, Hamid R. Mirshahidi, Jordi Rodon Ahnert, Frank J. Brescia, Olwen Hahn, Jane M. Raymond, David D. Biggs, Roisin M. Connolly, Elad Sharon, Larissa A. Korde, Robert J. Gray, Edward Mayerson, Melissa Plets, Charles D. Blanke, Young Kwang Chae, Razelle Kurzrock
Institutions: NYU Langone Health, NYU Langone’s Laura and Isaac Perlmutter Cancer Center, New York University, Fred Hutch Cancer Center, Moores Cancer Center, Indiana University Health, Indiana University Indianapolis, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, University of Michigan, Dartmouth–Hitchcock Medical Center, Dartmouth Cancer Center, Harold C. Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Kaiser Permanente, Kaiser Permanente San Diego Medical Center, The University of Kansas Health System, Loma Linda University Medical Center, Loma Linda University, The University of Texas MD Anderson Cancer Center, Medical University of South Carolina, MUSC Hollings Cancer Center, University of Chicago, University of Chicago Medicine Comprehensive Cancer Center, Allegheny General Hospital, Johns Hopkins University, Sidney Kimmel Comprehensive Cancer Center, National Cancer Institute, Dana-Farber Cancer Institute, Oregon Health & Science University, OHSU Knight Cancer Institute, Northwestern University
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4361814516