LBA1 - Denosumab added to 2 different nab-paclitaxel regimens as neoadjuvant therapy in patients with primary breast cancer: Time to event analysis from the GeparX 2 × 2 randomized clinical trial

Background

GeparX (NCT02682693) investigated denosumab (Dmab) alongside anthracycline/taxane-based neoadjuvant chemotherapy (NACT) and two different nab-paclitaxel (nabP) schedules. Weekly nabP showed higher pathological complete response (pCR) rates, while adding Dmab did not.

Methods

Patients (pts; n=780) were randomized in a 2x2 fashion to either receive Dmab (120 mg s.c. q4w for 6 cycles) or none and to receive nabP (125 mg/m²) either weekly or d1+8 q3w each for 12 weeks. Pts with TNBC received additional carboplatin, and pts with HER2+ BC received trastuzumab biosimilar ABP980 for 8 cycles and pertuzumab for at least 4 cycles. All pts subsequently received standard epirubicin/cyclophosphamide for 4 cycles. This is the preplanned analysis of invasive disease-free survival (iDFS), distant disease-free survival (DDFS) and overall survival (OS).

Results

After a median follow-up of 62.3 months, no significant difference in iDFS was observed between pts receiving Dmab or none (HR= 0.87, 95% CI 0.62–1.21; p=0.39) or between different nabP schedules (HR= 0.87, 95% CI 0.62–1.21; p=0.41). Pts receiving Dmab had numerically longer DDFS although not reaching statistical significance with a HR of 0.77 (CI 0.54, 1.1) p=0.16 and an estimated 5y DDFS of 85.8% with vs 80.2% without Dmab. A trend for a higher DDFS with vs without Dmab in the pCR group HR 0.46 (CI 0.21, 1.01) p=0.054 also did not reach significance. No significant differences in OS between pts receiving or not receiving Dmab or between different nabP schedules were detected. Overall, absence of pCR at surgery was associated with a poorer outcome with 5y rates for iDFS 73.9% vs 87.8%, DDFS 76.1% vs 91.6% and OS 86.2% vs 95.4% in pts without vs with pCR. No unexpected long-term toxicities were noted.

Conclusions

This is the first randomized trial to report long-term outcomes for the addition of Dmab to anthracycline/taxane-based neoadjuvant therapy. Although there were numerically less distant relapses with Dmab, this did not reach statistical significance. Despite the observed increase in pCR with nabP weekly, this did not translate into an improved long-term outcome.

Clinical trial identification

NCT02682693.

Legal entity responsible for the study

German Breast Group, GBG Forschungs GmbH.

Funding

Amgen and BMS (Celgene).

Disclosure

S. Loibl: Other, Grants and other support: AbbVie, AstraZeneca, Celgene; Other support: Amgen, BMS, Eirgenix, Eisai Europe Ltd., GSK, Lilly, Merck, Pierre Fabre, Relay Therapeutics, Sanofi; Other, Grants, non-financial support, and other support: Daiichi Sankyo, Immunomedics/Gilead, Novartis, Pfizer, Roche; Other, Grants: Molecular Health; Other, non-financial support and other support: Seagen; Other support from Olema outside the submitted work: Olema; Other, Dr Loibl has a patent for EP14153692.0 pending, a patent for EP21152186.9 pending, a patent for EP15702464.7 issued, a patent for EP19808852.8 pending, and a patent for Digital Ki67 Evaluator issued and licensed: Patent. M. Reinisch: Financial Interests, Personal, Other, Honoraria: Pfizer, Novartis, Lilly, Roche Pharma AG, AstraZeneca, Daiichi-Sankyo, Somatex, Seagen, Pfizer, Gilead; Financial Interests, Personal, Advisory Role: Roche Pharma AG, Daiichi Sankyo, Lilly, Novartis, Seagen, Pfizer, Somatex, Gilead, AstraZeneca, MSD Oncology. M. Just: Other, Institutional, Other, Honoraria: AstraZeneca, Art tempi, Daiichi Sankyo, Pfizer, Sanofi-Aventis, Myriad; Other, Institutional, Other, Honoraria, Consulting or Advisory Role: Amgen, Lilly, Roche, MSD Oncology Pierre Fabre, Seagen, Gilead, Novartis, Stemline; Other, Institutional, Other, Consulting or Advisory Role: Agendia, Lily, Genzyme. M. Untch: Other, Speaker’s Bureau: AstraZeneca, Novartis, Roche, Aristo Pharma. A. Schneeweiss: Financial Interests, Personal and Institutional, Research Grant: Celgene, Roche, AbbVie; Financial Interests, Personal, Other, Travel expenses: Celgene, Roche, Lilly, AstraZeneca; Financial Interests, Personal, Other, Honoraria: Roche, Celgene, Pfizer, AstraZeneca, Novartis, MSD, Tesaro, Pfizer, Seagen, Gilead, GSK, Bayer, Amgen, Pierre Fabre. S. Seiler: Financial Interests, Institutional, Research Grant: Daiichi Sankyo, Gilead, Novartis, Pfizer, Roche, Seagen, AbbVie, AstraZeneca, BMS, Molecular Health, Novartis. M. Thill: Other, Advisory Board: Agendia, Amgen, AstraZeneca, Aurikamed, Becton/Dickinson, Biom‘Up, ClearCut, Clovis, Daiichi Sankyo, Eisai, Exact Sciences, Gilead Science, Grünenthal, GSK, Lilly, MSD, Neodynamics, Novartis, Onkowissen, Organon, Pfizer, PFM Medical, Pierre Fabre, Roche; Other, Manuscript support: Amgen, ClearCut, Clovis, Organon, PFM medical, Roche, Servier; Other, Travel expenses: Amgen, Art Tempi, AstraZeneca, Clearcut, Clovis, Connect Medica, Daiichi Sankyo, Eisai, Exact Sciences, Gilead, Hexal, I-Med-Institute, Lilly, MCI, MSD, Neodynamics, Novartis, Pfizer, PFM Medical, Roche, RTI Surgical, Seagen; Other, Congress support: Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Gilead, Hexal, Lilly, Neodynamics, Novartis, Pfizer, Pierre Fabre, Roche, Sirius Medical; Other, Lecture honoraria: Amgen, Art Tempi, AstraZeneca, Clovis, Connect Medica, Eisai, Exact Sciences, Gedeon Richter, Gilead Science, GSK, Hexal, I-Med-Institute, Jörg Eickeler, Laborarztpraxis Walther et al., Lilly, MCI, Medscape, MSD, Medtronic, Novartis, Onkowissen, Pfizer; Other, Funding, Trial funding: Endomag, Exact Sciences; Other, Trial honoraria: AstraZeneca, Biom’Up, Celgene, Clearcut, Neodynamics, Novartis, PFM medical, Roche, RTI Surgical. C. Solbach: Financial Interests, Personal, Invited Speaker, Honoraria: Pfizer, Novartis, MSD, Roche, Gedeon Richter; Financial Interests, Personal, Invited Speaker: Samsung; Financial Interests, Personal, Advisory Role: Roche, Daiichi Sankyo Europe GmbH; Financial Interests, Personal, Speaker’s Bureau: Eickler, MedConcept, Dialog Service GmbH; Financial Interests, Personal, Other, Travel, Accommodation, Expenses: Pfizer, Roche, Novartis, Samsung. N. Filmann: Financial Interests, Institutional, Research Grant: Daiichi Sankyo, Gilead, Novartis, Pfizer, Roche, AbbVie, AstraZeneca, BMS. J. Holtschmidt: Other, personal fees and non-financial support: Daiichi Sankyo; Other, non-financial support: Hologic; Other, personal fees: MSD Oncology, Novartis, Palleos Health care, Pfizer, Roche Pharma, Seagen; Other, employee: GBG Forschungs GmbH; Financial Interests, Institutional, Funding, research funding: AbbVie, AstraZeneca, BMS, Daiichi Sankyo, Gilead, Novartis, Pfizer and Roche; Non-Financial Interests, Institutional, Other, medical writing: Daiichi Sankyo, Gilead, Novartis, Pfizer, Roche and Seagen; Other, GBG Forschungs GmbH has following royalties/patents: EP14153692.0, EP21152186.9, EP15702464.7, EP19808852.8 and VM Scope GmbH: Patents. J. Blohmer: Financial Interests, Personal, Invited Speaker, Honoraria: AstraZeneca, Daiichi Sankyo, Eisai, Gilead, MSD, Lilly, Novartis, Pfizer, Roche, Seagen; Financial Interests, Personal, Other, Support for attending meeting and/or travel: AstraZeneca, Daiichi Sankyo, Gilead, Pfizer, Roche; Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Eisai, Gilead, MSD, Lilly, Novartis, Pfizer, Roche, Seagen. T. Link: Other, Honoraria: Amgen, Roche, MSD, Novartis, Pfizer, Lilly, GSK, Gilead, AstraZeneca, Daiichi Sankyo, Stemline; Other, Advisory Board, Participant: MSD, Roche, Pfizer, Lilly, Myriad, Eisai, GSK, Gilead, Daiichi Sankyo. All other authors have declared no conflicts of interest.