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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)
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Supplemental Figure 1: CONSORT Diagram
Supplemental Table 1: Clinical and tumor characteristics of long-term responders
Date
2021-10-29
Authors
Adams, Sylvia
Othus, Megan
Patel, Sandip Pravin
Miller, Kathy D.
Chugh, Rashmi
Schuetze, Scott M.
Chamberlin, Mary D.
Haley, Barbara J.
Storniolo, Anna Maria V.
Reddy, Mridula P.
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Publisher
American Association for Cancer Research
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Abstract
Purpose: Metaplastic breast cancer (MpBC) is a rare aggressive subtype that responds poorly to cytotoxics. Median survival is approximately eight months for metastatic disease. We report results for advanced MpBC treated with ipilimumab+nivolumab, a cohort of S1609 for rare cancers (DART: NCT02834013). Methods: Prospective, open-label, multicenter phase II (two-stage) trial of ipilimumab (1mg/kg IV q6weeks) plus nivolumab (240mg IV q2weeks) 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, 2 (0-5). ORR was 18%; 3/17 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 (AEs), including one grade 5 AE. Eight patients (47%) developed an immune-related AE (irAE); with adrenal insufficiency observed in all three responders. Responses occurred in tumors with low tumor mutational burden, low PD-L1 and absent TILs. Conclusion: 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.
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Keywords
Metaplastic breast cancer , Rare tumors , S1609 , DART , Ipilimumab , Nivolumab
Citation
Adams, S., Othus, M., Patel, S. P., Miller, K. D., Chugh, R., Schuetze, S. M., Chamberlin, M. D., Haley, B. J., Storniolo, A. M. V., Reddy, M. P., Anderson, S. A., Zimmerman, C. T., O'Dea, A.P., Mirshahidi, H. R., Rodon Ahnert, J., Brescia, F. J., Hahn, O., Raymond, J. M., Biggs, D. D., Connolly, R. M., Sharon, E., Korde, L. A., Gray, R. J., Mayerson, E., Plets, M., Blanke, C. D., Chae, Y. K., Kurzrock, R. A (2021) '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)', Clinical Cancer Research. doi: 10.1158/1078-0432.CCR-21-2182
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© 2021, American Association for Cancer Research.