A randomized phase 2 study of neoadjuvant carboplatin and paclitaxel with or without atezolizumab in triple negative breast cancer (TNBC) - NCI 10013

dc.contributor.authorAdemuyiwa, Foluso O.
dc.contributor.authorGao, Feng
dc.contributor.authorStreet, Cherease R.
dc.contributor.authorChen, Ina
dc.contributor.authorNorthfelt, Donald W.
dc.contributor.authorWesolowski, Robert
dc.contributor.authorArora, Mili
dc.contributor.authorBrufsky, Adam
dc.contributor.authorDees, E. Claire
dc.contributor.authorSanta-Maria, Cesar A.
dc.contributor.authorConnolly, Roisin M.
dc.contributor.authorForce, Jeremy
dc.contributor.authorMoreno-Aspitia, Alvaro
dc.contributor.authorHerndon, John M.
dc.contributor.authorCarmody, Madelyn
dc.contributor.authorDavies, Sherri R.
dc.contributor.authorLarson, Sarah
dc.contributor.authorPfaff, Kathleen L.
dc.contributor.authorJones, Stephanie M.
dc.contributor.authorWeirather, Jason L.
dc.contributor.authorGiobbie-Hurder, Anita
dc.contributor.authorRodig, Scott J.
dc.contributor.authorLiu, Zheng
dc.contributor.authorHagemann, Ian S.
dc.contributor.authorSharon, Elad
dc.contributor.authorGillanders, William E.
dc.contributor.funderNational Cancer Instituteen
dc.description.abstractAtezolizumab with chemotherapy has shown improved progression-free and overall survival in patients with metastatic PD-L1 positive triple negative breast cancer (TNBC). Atezolizumab with anthracycline- and taxane-based neoadjuvant chemotherapy has also shown increased pathological complete response (pCR) rates in early TNBC. This trial evaluated neoadjuvant carboplatin and paclitaxel with or without atezolizumab in patients with clinical stages II-III TNBC. The co-primary objectives were to evaluate if chemotherapy and atezolizumab increase pCR rate and tumor infiltrating lymphocyte (TIL) percentage compared to chemotherapy alone in the mITT population. Sixty-seven patients (ages 25–78 years; median, 52 years) were randomly assigned – 22 patients to Arm A, and 45 to Arm B. Median follow up was 6.6 months. In the modified intent to treat population (all patients evaluable for the primary endpoints who received at least one dose of combination therapy), the pCR rate was 18.8% (95% CI 4.0–45.6%) in Arm A, and 55.6% (95% CI 40.0–70.4%) in Arm B (estimated treatment difference: 36.8%, 95% CI 8.5–56.6%; p = 0.018). Grade 3 or higher treatment-related adverse events occurred in 62.5% of patients in Arm A, and 57.8% of patients in Arm B. One patient in Arm B died from recurrent disease during the follow-up period. TIL percentage increased slightly from baseline to cycle 1 in both Arm A (mean ± SD: 0.6% ± 21.0%) and Arm B (5.7% ± 15.8%) (p = 0.36). Patients with pCR had higher median TIL percentages (24.8%) than those with non-pCR (14.2%) (p = 0.02). Although subgroup analyses were limited by the small sample size, PD-L1-positive patients treated with chemotherapy and atezolizumab had a pCR rate of 75% (12/16). The addition of atezolizumab to neoadjuvant carboplatin and paclitaxel resulted in a statistically significant and clinically relevant increased pCR rate in patients with clinical stages II and III TNBC.en
dc.description.sponsorshipNational Cancer Institute (Cancer Therapy Evaluation Program)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.identifier.citationAdemuyiwa, F. O., Gao, F., Street, C. R., Chen, I., Northfelt, D. W., Wesolowski, R., Arora, M., Brufsky, A., Dees, E. C., Santa-Maria, C. A., Connolly, R. M., Force, J., Moreno-Aspitia, A., Herndon, J. M., Carmody, M., Davies, S. R., Larson, S., Pfaff, K. L., Jones, S. M., Weirather, J. L., Giobbie-Hurder, A., Rodig, S. J., Liu, Z., Hagemann, I. S., Sharon, E. and Gillanders, W. E. (2022) 'A randomized phase 2 study of neoadjuvant carboplatin and paclitaxel with or without atezolizumab in triple negative breast cancer (TNBC) - NCI 10013', npj Breast Cancer, 8(1), 134 (11pp). doi: 10.1038/s41523-022-00500-3en
dc.identifier.journaltitlenpj Breast Canceren
dc.publisherSpringer Nature Limiteden
dc.rights© 2022, the Authors. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.en
dc.subjectNeoadjuvant carboplatinen
dc.subjectTriple negative breast canceren
dc.subject(TNBC) - NCI 10013en
dc.titleA randomized phase 2 study of neoadjuvant carboplatin and paclitaxel with or without atezolizumab in triple negative breast cancer (TNBC) - NCI 10013en
dc.typeArticle (peer-reviewed)en
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