Survival analysis of the randomised phase III GeparOcto trial comparing neoadjuvant chemotherapy of intense dose-dense epirubicin, paclitaxel, cyclophosphamide versus weekly paclitaxel, liposomal doxorubicin (plus carboplatin in triple-negative breast cancer) for patients with high-risk early breast cancer.

BACKGROUND

GeparOcto demonstrated that pathological complete response (pCR) of intense dose-dense epirubicin, paclitaxel and cyclophosphamide (iddEPC) was comparable to weekly paclitaxel/non-pegylated liposomal doxorubicin (plus carboplatin (PM(Cb) in triple-negative breast cancer [TNBC]) in high-risk early breast cancer (BC). Here, we report time-to-event secondary end-points.

PATIENTS AND METHODS

Patients were randomised to receive 18 weeks of E (150 mg/m

RESULTS

945 patients started treatment (iddEPC n = 470; PM(Cb) n = 475). After a median follow-up of 47.0 (range 1.6-61.5) months, 162 (75 in iddEPC; 87 in PM(Cb)) invasive disease-free survival (iDFS) events and 79 (41 in iddEPC; 38 in PM(Cb)) deaths were reported. No significant difference was observed in 4-year iDFS (81.9% iddEPC versus 79.7% PM(Cb), HR = 1.16 [95%CI 0.85-1.59], log-rank p = 0.334) or 4-year overall survival (OS) (90.3% iddEPC versus 90.6% PM(Cb), HR = 0.90 [95%CI 0.58-1.40], log-rank p = 0.637) overall and in HER2+ and TNBC subgroups. HR+/HER2- BC patients, however, had significantly better 4-year iDFS (77.9% iddEPC versus 62.5% PM, HR = 2.11 [95%CI 1.08-4.10], log-rank p = 0.025) and 4-year OS with iddEPC (94.7% iddEPC versus 80.1% PM, HR = 3.26 [95%CI 1.06-10.00], log-rank p = 0.029).

CONCLUSION

While there was no difference in survival for the entire cohort, the HR+/HER2-subgroup significantly benefits from iddEPC. This supports the concept of an additional effect of NACT beyond pCR in patients with HR+/HER2- BC. CLINICALTRIALS.

GOV IDENTIFIER

NCT02125344.

Informations de copyright

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Déclaration de conflit d'intérêts

Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AS reports grants from Celgene, grants from Roche, grants from AbbVie, personal fees from Roche, personal fees from AstraZeneca, personal fees from Celgene, personal fees from Roche, personal fees from Roche, personal fees from Celgene, personal fees from Pfizer, personal fees from AstraZeneca, personal fees from Novartis, personal fees from MSD, personal fees from Tesaro, personal fees from Lilly, personal fees from Pfizer, other from Roche, outside the submitted work; CD reports grants from European Commission H2020, grants from German Cancer Aid Translational Oncology, during the conduct of the study; personal fees from Novartis, personal fees from Roche, personal fees from MSD Oncology, personal fees from Daiichi Sankyo, personal fees from AstraZeneca, from Molecular Health, grants from Myriad, personal fees from Merck, other from Sividon diagnostics, outside the submitted work; In addition, Dr. Denkert 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; CH reports a consulting or advisory role for Roche, AstraZeneca, Novartis, Lilly-Pharma, Celgene; CJ reports personal fees from Roche, personal fees from Celgene, personal fees from AstraZeneca, during the conduct of the study; CS reports a consulting or advisory role for Hologicm, MSD; reports travel, accommodations, or expenses from Pfizer, MSD, AstraZeneca, Roche; EH reports honoraria and a consulting or advisory role from AstraZeneca; HT reports other from Pierre Fabre, other from Pfizer Pharma, other from Mundipharma, other from ClinSol, other from Novartis, other from Lilly, other from AMGEN, other from Grünenthal, other from Vifor, other from AstraZeneca, other from Mylan, other from BMS, during the conduct of the study; JH reports personal fees from Lilly, personal fees from Novartis, personal fees from Pfizer, personal fees from Abbvie, personal fees from Astra Zeneca, personal fees from MSD, personal fees from Celgene, personal fees from Roche, other from Daichii, other from Roche, other from Pfizer, grants from Novartis, grants from Hexal, outside the submitted work; JUB reports honoraria, travel support and unrestricted grants from AMGEN, AstraZeneca, Lilly, Molecular Health, MSD, Novartis, Pfizer, Pierre-Fabre, Roche; KK reports other from MSD Sharpe amd Dome GmBH, personal fees from Roche, personal fees from Pfizer, personal fees from Astra Zeneca, outside the submitted work; KL reports a consulting or advisory role for Roche, Novartis, Pfizer, Lilly, Exact Science Eisai, MSD; reports travel, accommodations, or expenses from Roche; KR reports personal fees from AstraZeneca, personal fees from Pfizer, personal fees from MSD, outside the submitted work; LM reports honoraria from Pfizer, Eisai, AstraZeneca, Roche, Lilly; reports a consulting or advisory role for Pfizer, Roche, Eisai, AstraZeneca; reports travel, accommodations, or expenses from Eisai, Pfizer, AstraZeneca, Lilly, and Roche; MU reports honoraria to the employer/institution from Amgen, Astra Zeneca, Celgene, Daiichi Sankyo, Lilly, Roche, Pfizer, Pierre Fabre, Sanofi-Aventis, MSD; reports research funding to the employer/institution from Amgen, Astra Zeneca, Celgene, Daiichi Sankyo, Lilly, Pfizer, Roche, Sanofi Aventis, Pierre Fabre; PAF reports honoraria from Roche, Novartis, Pfizer, Daiichi-Sankyo, Eisai, Merck Sharp & Dohme, Astra Zeneca, Hexal, Lilly, Pierre Fabre, Seagen, Agendia, Cepheid, BionTech; reports a consulting or advisory role for Roche, Novartis, Pfizer, Daiichi-Sankyo, Eisai, Merck Sharp & Dohme, Astra Zeneca, Hexal, Lilly, Pierre Fabre, Seagen, Agendia, Lilly; reports research funding from Novartis, BioNTech AG, Cepheid; SL reports honoraria from Abbvie, Amgen, AstraZeneca, Bayer, BMS, Celgene, DSI, Eirgenix, GSK, Lilly, Merck, Novartis, Pfizer, Pierre Fabre, Prime/Medscape, Puma, Roche, Samsung, and Seagen; reports a consulting or advisory role for Abbvie, Amgen, AstraZeneca, Bayer, BMS, Celgene, DSI, Eirgenix, GSK, Lilly, Merck, Novartis, Pfizer, Pierre Fabre, Prime/Medscape, Puma, Roche, and Seagen; reports a speaker's bureau for AstraZeneca, DSI, Novartis, Pfizer, Pierre Fabre, Prime/Medscape, Roche, and Samsung; reports research funding from Abbvie, Amgen, AstraZeneca, Celgene, Cepheid, DSI, Immunomedics, Novartis, Pfizer, and Roche; reports a patent or intellectual property interest with VM Scope GmbH; reports another relationship with Roche; TL reports honoraria from Amgen, Roche, Clovis, MSD, Novartis, Pfizer, Lilly; reports a consulting or advisory role from Tesaro, Amgen, MSD, Roche, Pfizer, Lilly, Myriad, Esai, GSK; reports travel, accommodations, or expenses from MSD, Celgen, Clovis; VM reports and Speaker honoraria received from Amgen, AstraZeneca, Celgene, Roche, Teva. Consultancy honoraria from Roche, Amgen, Tesaro and Myelo Therapeutics; No other potential conflict of interest relevant to this article was reported.