160O - Survival analysis of the randomized phase III GeparOcto trial comparing neoadjuvant chemotherapy (NACT) of iddEPC versus weekly paclitaxel, liposomal doxorubicin (plus carboplatin in triple-negative breast cancer, TNBC) (PM(Cb)) for patients (pts) with high-risk early breast cancer (BC)

Background

GeparOcto investigated dose-dense NACT with intense dose-dense epirubicin, paclitaxel, cyclophosphamide (iddEPC) and PM(Cb) in high-risk early BC. Primary endpoint pathological complete response (pCR; ypT0/is ypN0) was comparable in the whole cohort as well as in subgroups (Schneeweiss et al. EJC 2019). Here, we report the secondary endpoints invasive disease-free survival (iDFS) and overall survival (OS).

Methods

Pts were randomized (stratified by BC subtype, Ki67, lymphocyte-predominant BC) to receive 18 weeks of E (150 mg/m²) followed by P (225 mg/m²) followed by C (2000 mg/m²), each q2w for 3 cycles or weekly P (80 mg/m²) plus M (20 mg/m²) plus, in TNBC, Cb (AUC 1.5). HER2+ BC pts additionally received trastuzumab (6 [loading dose 8]mg/kg q3w) and pertuzumab (420 [840]mg q3w) with all P and C cycles. Adjuvant locoregional and endocrine therapy were given according to national guidelines. Secondary time-to-event endpoints were iDFS and OS.

Results

Between 12/2014 and 06/2016, a total of 961 pts were randomized and 945 started treatment (iddEPC n=470, PM(Cb) n=475). After a median follow-up of 47.0 (range 1.6-61.5) months, 75 iDFS events in iddEPC and 87 in PM(Cb) were reported. Overall, there was no difference in iDFS (hazard ratio PM(Cb) to iddEPC 1.16, 95%CI 0.85-1.59, p=0.3357) or OS (hazard ratio 0.90, 95%CI 0.58-1.40, p=0.6371) between both arms. In the subgroup of hormone-receptor (HR)+/HER2- BC, iDFS was significantly longer for iddEPC (4-year iDFS 62.5% with PM vs.77.9% with iddEPC; hazard ratio 2.11, 95%CI 1.08-4.10, p=0.0284), translating into an OS benefit (4-year OS 80.1% vs. 94.7%; hazard ratio 3.26, 95%CI 1.06-10.00, p=0.0388). There was no significant difference in survival in HER2+ or TNBC.

Conclusions

While there was no difference in survival following NACT with iddEPC or PM(Cb) for the entire cohort, the subgroup of HR+/HER2- BC significantly benefits from treatment with iddEPC. This supports the concept of effective therapy beyond pCR in luminal BC pts.

Clinical trial identification

NCT02125344.

Editorial acknowledgement

Dr. Bianca Lederer, GBG Forschungs GmbH.

Legal entity responsible for the study

GBG Forschungs GmbH.

Funding

Amgen, Roche, Teva.

Disclosure

A. Schneeweiss: Research grant/Funding (self): Celgene; Research grant/Funding (self): Roche; Research grant/Funding (self): AbbVie; Research grant/Funding (self): Molecular Partner; Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: AstraZeneca; Travel/Accommodation/Expenses: Celgene; Travel/Accommodation/Expenses: Roche; Honoraria (self): Roche; Honoraria (self): Celgene; Honoraria (self): Pfizer; Honoraria (self): AstraZeneca; Honoraria (self): Novartis; Honoraria (self): MSD; Honoraria (self): Tesaro; Honoraria (self): Lilly; Travel/Accommodation/Expenses: Pfizer; Research grant/Funding (self), Medical writing grant: Roche. V. Möbus: Advisory/Consultancy: Roche; Advisory/Consultancy: Clovis; Advisory/Consultancy: Myelotherapeutics; Travel/Accommodation/Expenses: Celgene. H. Tesch: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis. C. Denkert: Shareholder/Stockholder/Stock options: Sividon Diagnostics; Honoraria (self): Novartis; Honoraria (self), Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: MSD Oncology; Advisory/Consultancy: Daiichi Sankyo; Research grant/Funding (institution): Myriad Genetics; Licensing/Royalties: VMScope digital pathology software; Licensing/Royalties: Patent application: EP18209672 - cancer immunotherapy; Licensing/Royalties: Patent application EP20150702464 - therapy response; Licensing/Royalties: Patent application EP20150702464 - therapy response. C. Hanusch: Honoraria (self): Roche; Honoraria (self): Celgene; Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): AstraZeneca; Honoraria (self): Lilly. T. Link: Non-remunerated activity/ies: Pharma Mar; Non-remunerated activity/ies: Daiichi Sankyo; Honoraria (self), Non-remunerated activity/ies: MSD; Honoraria (self): Amgen; Honoraria (self), Non-remunerated activity/ies: Pfizer; Honoraria (self): Novartis; Honoraria (self): Teva; Honoraria (self): Tesaro; Honoraria (self), Non-remunerated activity/ies: Roche; Honoraria (self), Non-remunerated activity/ies: Clovis; Non-remunerated activity/ies: Celgene. M. Untch: Honoraria (institution), Non-remunerated activity/ies: AbbVie; Honoraria (institution), Non-remunerated activity/ies: Amgen GmbH; Honoraria (institution), Non-remunerated activity/ies: AstraZeneca; Honoraria (institution): BMS; Honoraria (institution), Non-remunerated activity/ies: Celgene GmbH ; Honoraria (institution), Non-remunerated activity/ies: Daiichi Sankyo ; Honoraria (institution), Non-remunerated activity/ies: Eisai GmbH; Honoraria (institution): Lilly Deutschland; Honoraria (institution), Non-remunerated activity/ies: Lilly Int.; Honoraria (institution), Non-remunerated activity/ies: MSD Merck; Honoraria (institution), Non-remunerated activity/ies: Mundipharma; Honoraria (institution), Non-remunerated activity/ies: Myriad Genetics ; Honoraria (self), Non-remunerated activity/ies: Odonate; Honoraria (institution), Non-remunerated activity/ies: Pfizer GmbH; Honoraria (self): PUMA Biotechnology; Honoraria (institution), Non-remunerated activity/ies: Roche Pharma AG; Honoraria (institution), Non-remunerated activity/ies: Sanofi Aventis Deutschland GmbH; Honoraria (institution), Non-remunerated activity/ies: TEVA Pharmaceuticals Ind Ltd; Honoraria (institution), Non-remunerated activity/ies: Novartis; Honoraria (institution): Pierre Fabre; Honoraria (institution), Non-remunerated activity/ies: Clovis Oncology. C. Jackisch: Honoraria (self): Celgene; Honoraria (self): Roche. J-U. Blohmer: Honoraria (self): Amgen; Honoraria (self): AstraZeneca; Honoraria (self): MSD Oncology; Honoraria (self): Novartis/Pfizer; Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self): SonoScape. P.A. Fasching: Speaker Bureau/Expert testimony: Amgen; Advisory/Consultancy: Roche; Research grant/Funding (institution): BionTech; Advisory/Consultancy: Roche; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Celgene; Speaker Bureau/Expert testimony: Daiichi-Sankyo; Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck Sharp & Dohme; Advisory/Consultancy: Macrogenics; Advisory/Consultancy: Eisai; Advisory/Consultancy: Puma; Research grant/Funding (institution): Cepheid; Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Advisory/Consultancy, Research grant/Funding (institution): Novartis; Advisory/Consultancy: AstraZeneca; Speaker Bureau/Expert testimony: Amgen. J. Huober: Honoraria (self): Lilly; Honoraria (self): Roche; Honoraria (self), Research grant/Funding (self): Novartis; Honoraria (self): Pfizer; Travel/Accommodation/Expenses: AbbVie; Honoraria (self): AstraZeneca; Honoraria (self), Research grant/Funding (self), Travel/Accommodation/Expenses: Celgene; Research grant/Funding (self): Hexal; Honoraria (self): MSD; Travel/Accommodation/Expenses: Daiichi. K.E. Rhiem: Honoraria (self): AstraZeneca; Honoraria (self): Tesaro; Honoraria (self): Pfizer. K. Lübbe: Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy: Genomic Health; Honoraria (self): Pfizer. S. Loibl: Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Amgen; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Celgene; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Novartis; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Roche; Honoraria (institution), Advisory/Consultancy: Seattle Genetics; Honoraria (institution), Advisory/Consultancy: PriME/ Medscape; Speaker Bureau/Expert testimony: Chugai; Research grant/Funding (institution): Teva; Research grant/Funding (institution): Vifor; Honoraria (institution), Research grant/Funding (institution): Daiichi-Sankyo; Honoraria (institution), Advisory/Consultancy: Lilly; Honoraria (institution), Advisory/Consultancy: Samsung; Advisory/Consultancy: Eirgenix; Advisory/Consultancy: BMS; Advisory/Consultancy: Puma; Honoraria (institution): MSD; Research grant/Funding (institution): Immunomedics; Licensing/Royalties, Immunsignature in TNBC: EP14153692.0 pending. All other authors have declared no conflicts of interest.