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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dc.check.date2022-10-29
dc.check.infoAccess to this article is restricted until 12 months after publication by request of the publisher.en
dc.contributor.authorAdams, Sylvia
dc.contributor.authorOthus, Megan
dc.contributor.authorPatel, Sandip Pravin
dc.contributor.authorMiller, Kathy D.
dc.contributor.authorChugh, Rashmi
dc.contributor.authorSchuetze, Scott M.
dc.contributor.authorChamberlin, Mary D.
dc.contributor.authorHaley, Barbara J.
dc.contributor.authorStorniolo, Anna Maria V.
dc.contributor.authorReddy, Mridula P.
dc.contributor.authorAnderson, Scott A.
dc.contributor.authorZimmerman, Collin T.
dc.contributor.authorO'Dea, Anne P.
dc.contributor.authorMirshahidi, Hamid R.
dc.contributor.authorRodon Ahnert, Jordi
dc.contributor.authorBrescia, Frank J.
dc.contributor.authorHahn, Olwen
dc.contributor.authorRaymond, Jane M.
dc.contributor.authorBiggs, David D.
dc.contributor.authorConnolly, Roisin M.
dc.contributor.authorSharon, Elad
dc.contributor.authorKorde, Larissa A.
dc.contributor.authorGray, Robert J.
dc.contributor.authorMayerson, Edward
dc.contributor.authorPlets, Melissa
dc.contributor.authorBlanke, Charles D.
dc.contributor.authorChae, Young Kwang
dc.contributor.authorKurzrock, Razelle
dc.contributor.funderNational Cancer Instituteen
dc.contributor.funderNational Institutes of Healthen
dc.contributor.funderBristol-Myers Squibben
dc.date.accessioned2021-11-05T12:19:11Z
dc.date.available2021-11-05T12:19:11Z
dc.date.issued2021-10-29
dc.date.updated2021-11-05T11:14:01Z
dc.description.abstractPurpose: 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.en
dc.description.sponsorshipNational Institutes of Health (National Cancer Institute grant award numbers U10CA180888; U010CA180819, U10CA180820; U10CA180821; U10180868; U10CA180794; UG1CA233196)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationAdams, 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-21-2182en
dc.identifier.doi10.1158/1078-0432.CCR-21-2182en
dc.identifier.eissn1557-3265
dc.identifier.issn1078-0432
dc.identifier.journaltitleClinical Cancer Researchen
dc.identifier.urihttps://hdl.handle.net/10468/12147
dc.language.isoenen
dc.publisherAmerican Association for Cancer Researchen
dc.rights© 2021, American Association for Cancer Research.en
dc.subjectMetaplastic breast canceren
dc.subjectRare tumorsen
dc.subjectS1609en
dc.subjectDARTen
dc.subjectIpilimumaben
dc.subjectNivolumaben
dc.titleA 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)en
dc.typeArticle (peer-reviewed)en
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