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Randomized Controlled Trial
. 2022 Nov;33(11):1149-1158.
doi: 10.1016/j.annonc.2022.07.1940. Epub 2022 Aug 9.

Neoadjuvant durvalumab improves survival in early triple-negative breast cancer independent of pathological complete response

S Loibl  1 , A Schneeweiss  2 , J Huober  3 , M Braun  4 , J Rey  5 , J-U Blohmer  6 , J Furlanetto  5 , D-M Zahm  7 , C Hanusch  4 , J Thomalla  8 , C Jackisch  9 , P Staib  10 , T Link  11 , K Rhiem  12 , C Solbach  13 , P A Fasching  14 , V Nekljudova  5 , C Denkert  15 , M Untch  16 ; GBG and AGO-B
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Free article
Randomized Controlled Trial

Neoadjuvant durvalumab improves survival in early triple-negative breast cancer independent of pathological complete response

S Loibl et al. Ann Oncol. 2022 Nov.
Free article

Abstract

Background: Addition of immune checkpoint inhibitors to neoadjuvant chemotherapy (NACT) is a promising strategy in early breast cancer, but the optimal duration of therapy is currently unknown. In the GeparNuevo (NCT02685059) trial, addition of durvalumab to NACT as previously reported led to a moderate increase in pathological complete response (pCR) rate by an absolute 9% (P = 0.287).

Patients and methods: Patients with cT1b-cT4a-d triple-negative breast cancer (TNBC) received durvalumab 1.5 g or placebo every 4 weeks added to nab-paclitaxel 125 mg/m2 weekly for 12 weeks, followed by durvalumab/placebo every 4 weeks plus epirubicin/cyclophosphamide every 2 weeks followed by surgery. Durvalumab was not continued after surgery. The primary objective was pCR. Secondary endpoints included invasive disease-free survival (iDFS), distant disease-free survival (DDFS) and overall survival (OS).

Results: A total of 174 patients were randomised between June 2016 and October 2017. After a median follow-up of 43.7 months, 34 events had occurred. Despite a non-significant increase in the pCR rate, significant differences were observed for 3-year iDFS, DDFS and OS: iDFS was 85.6% with durvalumab versus 77.2% with placebo [hazard ratio (HR) 0.48, 95% confidence interval (CI) 0.24-0.97, stratified log-rank P = 0.036]; DDFS 91.7% versus 78.4% (HR 0.31, 95% CI 0.13-0.74, P = 0.005); OS 95.2% versus 83.5% (HR 0.24, 95% CI 0.08-0.72, P = 0.006). pCR patients had 3-year iDFS of 95.5% with durvalumab and 86.1% without (HR 0.22, 95% CI 0.05-1.06). In the non-pCR cohort 3-year iDFS was 76.3% versus 69.7% (HR 0.67, 95% CI 0.29-1.54). Multivariable analysis confirmed a durvalumab effect independent of the pCR effect. No new safety signals occurred.

Conclusions: Durvalumab added to NACT in TNBC significantly improved survival despite a modest pCR increase and no adjuvant component of durvalumab. Additional studies are needed to clarify the optimal duration and sequence of checkpoint inhibitors in the treatment of early TNBC.

Keywords: checkpoint inhibitor; durvalumab; early triple-negative breast cancer; neoadjuvant chemotherapy; survival.

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Conflict of interest statement

Role of funding sources The funders had no role in the collection, analysis or interpretation of the data, and had no access to the study data. The study statisticians (JR, VN) had access to the raw data. The report was reviewed by all authors. The sponsor (GBG Forschungs GmbH) has developed the study design and written the study protocol in collaboration with the members of the neoadjuvant sub-board of the German Breast Group (GBG) and AGO-B. The corresponding author had full access to all data in the study and had final responsibility for the decision to submit for publication. Disclosure MU reports personal fees and non-financial support from AbbVie, Amgen GmbH, AstraZeneca, Celgene GmbH, Daiji Sankyo, Eisai GmbH, Lilly Int., Merck Sharp & Dohme (MSD), Merck, Mundipharma, Myriad Genetics, Pfizer GmbH, Roche, Sanofi Aventis Deutschland GmbH, Teva, Novartis, Clovis Oncology; personal fees from Bristol Myers Squibb (BMS), Lilly Deutschland, Pierre Fabre, Seattle Genetics, Seagen, outside the submitted work. AS reports grants from Celgene, Roche, AbbVie; personal fees from Roche, AstraZeneca, Celgene, Pfizer, AstraZeneca, Novartis, MSD, Tesaro, Lilly, Pfizer; other from Roche, outside the submitted work. CD reports grants from European Commission H2020, German Cancer Aid Translational Oncology, German Breast Group, during the conduct of the study; personal fees from Novartis, Roche, MSD Oncology, Daiichi Sankyo, AstraZeneca, Molecular Health, Merck, grants from Myriad; other from Sividon Diagnostics, outside the submitted work; has a patent VMScope digital pathology software with royalties paid, a patent WO2020109570A1-cancer immunotherapy pending, and a patent WO2015114146A1 and WO2010076322A1-therapy response issued. SL reports grants and other from AbbVie, non-financial support and other from Amgen, grants and other from AstraZeneca, other from Bayer, other from BMS, grants and other from Celgene, personal fees from Chugai, grants, non-financial support and other from Daiichi Sankyo, other from EirGenix, other from GSK, grants, non-financial support and other from Immunomedics/Gilead, other from Lilly, other from Merck, grants, non-financial support and other from Novartis, grants, non-financial support and other from Pfizer, other from Pierre Fabre, other from Prime/Medscape, non-financial support and other from Puma, grants, non-financial support and other from Roche, other from Samsung, non-financial support and other from Seagen, outside the submitted work; has a patent EP14153692.0 pending, a patent EP21152186.9 pending, a patent EP15702464.7 issued, a patent EP19808852.8 pending and a patent Digital Ki67 Evaluator with royalties paid. PAF reports personal fees from Novartis, grants from BioNTech, personal fees from Pfizer, Daiichi Sankyo, AstraZeneca, Eisai, MSD, Lilly, Pierre Fabre, Seagen, Roche, Hexal, Agendia; grants from Cepheid, during the conduct of the study. JH reports personal fees and other from Pfizer, grants and personal fees from Novartis, Lilly; personal fees and other from Roche, personal fees from AbbVie, AstraZeneca, MSD, Eisai, Seagen, Gilead; grants and personal fees from Hexal; other from Daiichi, outside the submitted work. KR reports personal fees from AstraZeneca, MSD, Pfizer, outside the submitted work. TL reports personal fees and non-financial support from Roche, personal fees from Novartis, personal fees and non-financial support from Pfizer, personal fees from Tesaro, personal fees and non-financial support from MSD, personal fees from Amgen, personal fees from Clovis, non-financial support from Clegene, personal fees from Lilly, Myriad, GSK, Esai, outside the submitted work. JUB reports personal fees from Amgen, AstraZeneca, MSD, Novartis, Lilly, Pfizer, Exact Sciences, Molecular Health, Seagen, outside the submitted work. CH reports personal fees for lectures, presentations, speaker’s bureaus, manuscript writing or educational events from AstraZeneca, Roche, Novartis, Lilly and Pfizer. PS reports personal fees, non-financial support and other from AbbVie, Janssen-Cilag, Amgen, Novartis, Pfizer, Gilead; grants, personal fees, non-financial support and other from Celgene; grants from AstraZeneca, outside the submitted work. All other authors have declared no conflicts of interest. Data sharing

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