Carboplatin with or without nivolumab in metastatic triple-negative breast cancer: a randomized phase II trial

This multi-institutional randomized phase II clinical trial (NCT03414684) investigated the efficacy and safety of carboplatin plus nivolumab compared to carboplatin in metastatic triple-negative breast cancer (mTNBC). The primary endpoint was progression-free survival (PFS) in a modified intention-to-treat (mITT) population of patients with chemotherapy-naïve (i.e., first-line) mTNBC. Secondary endpoints included overall survival (OS), confirmed objective response rate, confirmed clinical benefit rate, time to and duration of confirmed objective response, safety, and tolerability. Clinical outcomes were evaluated in the PD-L1-positive subgroup ( ≥ 1% immune cells; SP142 clone) per central review. Biospecimens were collected for correlative analyses. 75 patients were enrolled and treated between 2/2018-9/2020. Among the mITT population (n = 62), median PFS was 4.2 months with carboplatin plus nivolumab vs 5.5 months with carboplatin. Median OS did not significantly differ between arms (16.8 vs 11.1 months, respectively). In PD-L1-positive mTNBC patients (n = 24), median PFS was 8.3 vs 4.7 months; median OS was 17.6 vs 10.7 months. Grade ≥3 adverse events occurred in 56.8% of patients in the combination arm and 65.8% in the carboplatin arm. Carboplatin plus nivolumab did not significantly improve PFS compared to carboplatin in patients overall; however, a trend toward improved outcomes was observed in PD-L1-positive mTNBC patients. High mutational burden, interferon-gamma signaling, early circulating tumor DNA reduction, low baseline serum thymidine kinase activity, and urea cycle dysregulation in the microbiome emerged as potential predictors of response to immune checkpoint inhibitors with platinum. Immune checkpoint inhibitors combined with chemotherapy have demonstrated significant benefits in treating triple-negative breast cancer (TNBC). In this study, the authors present results from a randomized phase II trial evaluating the platinum-based and DNA-damaging agent carboplatin in combination with nivolumab in patients with metastatic TNBC.

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Journal
Nature Communications
Published
2026-05-16
DOI
https://doi.org/10.1038/s41467-026-73085-1
Primary Topic
HER2/EGFR in Cancer Research
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article
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0.00

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article

Carboplatin with or without nivolumab in metastatic triple-negative breast cancer: a randomized phase II trial

Lincoln W. Pasquina, Anna Frey, Satabhisa Mukhopadhyay, Tathagata Dasgupta et al.
Nature Communications
HER2/EGFR in Cancer Research
article

Carboplatin with or without nivolumab in metastatic triple-negative breast cancer: a randomized phase II trial

Lincoln W. Pasquina, Anna Frey, Satabhisa Mukhopadhyay, Tathagata Dasgupta, Kai W. Wucherpfennig, Katelyn X. Li, Romualdo Barroso, Lynn Bi, Kevin Bi, Merrida Childress, S. Lo, Noah Graham, Victoria Attaya, Russell Petry, S. Schnitt, Ana C. Garrido-Castro, Andrew D. Cherniack, Hersh Gupta, Nancy U. Lin, Jeanna Walsh, Madhavi Toke, Thomas Kuntz, Sara M. Tolaney, Wendy Chen, Jihye Park, Ye Tian, Paulina Lange, Ashka Patel, Peter A. Kaufman, Ricardo Pastorello, Natalie Sinclair, Jett Crowdis, Eliezer Van Allen, Nadine Tung, Elizabeth A. Mittendorf, Yvonne Li, Nabihah Tayob, Sarah Sinclair, Meredith Faggen, Jennifer Ligibel, Caroline C. Block, Molly DiLullo, Robert Wesolowski, Amy J. Williams
article en

Abstract

This multi-institutional randomized phase II clinical trial (NCT03414684) investigated the efficacy and safety of carboplatin plus nivolumab compared to carboplatin in metastatic triple-negative breast cancer (mTNBC). The primary endpoint was progression-free survival (PFS) in a modified intention-to-treat (mITT) population of patients with chemotherapy-naïve (i.e., first-line) mTNBC. Secondary endpoints included overall survival (OS), confirmed objective response rate, confirmed clinical benefit rate, time to and duration of confirmed objective response, safety, and tolerability. Clinical outcomes were evaluated in the PD-L1-positive subgroup ( ≥ 1% immune cells; SP142 clone) per central review. Biospecimens were collected for correlative analyses. 75 patients were enrolled and treated between 2/2018-9/2020. Among the mITT population (n = 62), median PFS was 4.2 months with carboplatin plus nivolumab vs 5.5 months with carboplatin. Median OS did not significantly differ between arms (16.8 vs 11.1 months, respectively). In PD-L1-positive mTNBC patients (n = 24), median PFS was 8.3 vs 4.7 months; median OS was 17.6 vs 10.7 months. Grade ≥3 adverse events occurred in 56.8% of patients in the combination arm and 65.8% in the carboplatin arm. Carboplatin plus nivolumab did not significantly improve PFS compared to carboplatin in patients overall; however, a trend toward improved outcomes was observed in PD-L1-positive mTNBC patients. High mutational burden, interferon-gamma signaling, early circulating tumor DNA reduction, low baseline serum thymidine kinase activity, and urea cycle dysregulation in the microbiome emerged as potential predictors of response to immune checkpoint inhibitors with platinum. Immune checkpoint inhibitors combined with chemotherapy have demonstrated significant benefits in treating triple-negative breast cancer (TNBC). In this study, the authors present results from a randomized phase II trial evaluating the platinum-based and DNA-damaging agent carboplatin in combination with nivolumab in patients with metastatic TNBC.

Nature Communications
Broad Institute (US), Brigham and Women's Hospital (US), UMass Memorial Health Care (US), Program for Appropriate Technology in Health (US), Beth Israel Deaconess Medical Center (US), Harvard University (US), Viavi Solutions (United States) (US), University of Vermont Medical Center (US), Stamford Hospital (US), Eastern Maine Medical Center (US), Dana-Farber Cancer Institute (US), Dana-Farber/Harvard Cancer Center (US), Hospital Sírio-Libanês (BR), Sociedade Brasileira de Oncologia Clínica (BR), Dana-Farber Brigham Cancer Center (US), UMass Memorial Medical Center (US), Foundation Medicine (United States), The Ohio State University (US)
Conquer Cancer Foundation, Breast Cancer Research Foundation, Bristol-Myers Squibb, American Society of Clinical Oncology, Dana-Farber/Harvard Cancer Center, METAvivor, National Institutes of Health, Foundation Medicine, National Cancer Institute
Good health and well-being
Openalex Percentile: Top 6%
HER2/EGFR in Cancer Research
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