168MO - GeparX: Denosumab (Dmab) as add-on to different regimen of nab-paclitaxel (nP)-anthracycline based neoadjuvant chemotherapy (NACT) in early breast cancer (BC): Subgroup analyses by RANK expression and HR status

Background

In the GeparX trial, the addition of Dmab to NACT did not increase the pCR rate in early BC (41% vs. 43%; p=0.58) but nP q1 weekly (w) resulted in a significantly higher pCR rate than given d1, 8 q22 (45% vs. 39%; p=0.06; Blohmer et al. SABCS 2019). Here, we evaluated the pCR rates in different subgroups and in relation to RANK expression.

Methods

780 patients (pts) with high risk early BC were randomized 2x2 first to +/- Dmab (120mg sc q4w/6 cycles) and then to two different nP regimen (nP 125mg/m² q1w or d1, 8 q22) followed by EC (q2w or q3w) stratified by subtype, sTILs and EC regimen. Carboplatin was given in triple-negative (TNBC) and anti-HER2-therapy in HER2+ BC. RANK was stained on pre-therapeutic core biopsies (n=667) with the antibody RANK/Envision System HRP (DAB) and was analyzed immunohistochemically for percentage of membranous tumor cell staining (RANK high if >5 %).

Results

RANK expression was high in 20.8% of biopsies. It correlated with younger age (< 40 yrs: 15.5% low vs. 32.4% high; p<0.001), HR-status (ER and PR negative: 40.7% low vs. 69.1% high; p<0.001), tumor grade (G3: 63.6% low vs. 74.8 % high; p=0.03), Ki67 (>20%: 80.7% low vs. 91.4 % high; p=0.002) and stromal (s) TILs (>50% sTILs: 7.4% low vs. 10.8% high; p=0.002). High RANK expression resulted in a significantly higher pCR rate than RANK low (49.6% vs. 39.4%; p=0.037). But this was not associated with Dmab effect (RANK high: OR with vs. without Dmab 0.864 [90% CI 0.494-1.51], p=0.67; RANK low: OR 1.10 [90% CI 0.821-1.48], p=0.59; p interaction=0.53). pCR rates (ypT0 ypN0) are shown in the table. Table: 168MO

Conclusions

A high RANK expression was associated with significantly higher pCR rates (49.6% vs. 39.4%; p=0.037). This effect was pronounced in pts with luminal BC. However, a clinical benefit of Dmab in relation to RANK expression could not be shown. Further explorative analyses are still ongoing.

Clinical trial identification

NCT02682693.

Editorial acknowledgement

Legal entity responsible for the study

German Breast Group.

Funding

The trial was financially supported by Amgen and Celgene including drug supply.

Disclosure

T. Link: Non-remunerated activity/ies: PharmaMar; Non-remunerated activity/ies: Daiichi Sankyo; Honoraria (self), Non-remunerated ctivity/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; Non-remunerated activity/ies: Celgene; Honoraria (self), Non-remunerated activity/ies: Clovis. J-U. Blohmer: Honoraria (self): Amgen; Honoraria (self): AstraZeneca; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self): SonoScape. M. Untch: Honoraria (institution), Non-remunerated activity/ies, All fees to the institution/employer: AbbVie; Honoraria (institution), Non-remunerated activity/ies, All fees to the institution/employer: Amgen GmbH ; Honoraria (institution), Non-remunerated activity/ies, All fees to the institution/employer: AstraZeneca; Honoraria (institution), All fees to the institution/employer: BMS; Honoraria (institution), Non-remunerated activity/ies, All fees to the institution/employer: Celgene GmbH ; Honoraria (institution), Non-remunerated activity/ies, All fees to the institution/employer: Daiichi Sankyo ; Honoraria (institution), Non-remunerated activity/ies, All fees to the institution/employer: Eisai GmbH ; Honoraria (institution), All fees to the institution/employer: Lilly Deutschland; Honoraria (institution), Non-remunerated activity/ies, All fees to the institution/employer: Lilly Int.; Honoraria (institution), Non-remunerated activity/ies, All fees to the institution/employer: MSD Merck; Honoraria (institution), Non-remunerated activity/ies, All fees to the institution/employer: Mundipharma; Honoraria (institution), Non-remunerated activity/ies, All fees to the institution/employer: Myriad Genetics ; Honoraria (self), Non-remunerated activity/ies: Odonate; Honoraria (institution), Non-remunerated activity/ies, All fees to the institution/employer: Pfizer GmbH; Honoraria (self): PUMA Biotechnology; Honoraria (institution), Non-remunerated activity/ies, All fees to the institution/employer: Roche Pharma AG; Honoraria (institution), Non-remunerated activity/ies, All fees to the institution/employer: Sanofi Aventis Deutschland GmbH; Honoraria (institution), Non-remunerated activity/ies, All fees to the institution/employer: TEVA Pharmaceuticals Ind Ltd; Honoraria (institution), Non-remunerated activity/ies, All fees to the institution/employer: Novartis ; Honoraria (institution), All fees to the institution/employer: Pierre Fabre; Honoraria (institution), Non-remunerated activity/ies, All fees to the institution/employer: Clovis Oncology. P.A. Fasching: Speaker Bureau/Expert testimony, Lectures: Amgen; Advisory/Consultancy, Advisory Board: Roche; Research grant/Funding (institution): BionTech; Honoraria (self), Advisory/Consultancy, Advisory Board: Roche; Advisory/Consultancy, Advisory Board: Pfizer; Advisory/Consultancy, Advisory Board: Celgene; Speaker Bureau/Expert testimony, Lectures: Daiichi Sankyo; Advisory/Consultancy, Speaker Bureau/Expert testimony, Advisory Board, Lectures: Merck Sharp & Dohme; Advisory/Consultancy, Advisory Board: Macrogenics; Advisory/Consultancy, Advisory Board: Eisai; Advisory/Consultancy, Advisory Board: Puma; Research grant/Funding (institution), Research Support: Cepheid; Honoraria (self), Advisory Board; Lectures: Lilly; Advisory/Consultancy, Research grant/Funding (institution), Research Support; Advisory Board: Novartis; Advisory/Consultancy, Advisory Board: AstraZeneca; Speaker Bureau/Expert testimony, Lectures: Amgen. A. Schneeweiss: Research grant/Funding (institution), Research Grant: Celgene; Research grant/Funding (institution), Research Grant: Roche; Research grant/Funding (institution), Research Grant: AbbVie; Research grant/Funding (institution), Research Grant: Molecular Partner; Speaker Bureau/Expert testimony, Expert testimony: Roche; Speaker Bureau/Expert testimony, Expert testimony: AstraZeneca; Travel/Accommodation/Expenses, Travel expenses: Celgene; Travel/Accommodation/Expenses, Travel expenses: Roche; Honoraria (self), Honoraria: Roche; Honoraria (self), Honoraria: Celgene; Honoraria (self), Honoraria: Pfizer; Honoraria (self), Honoraria: AstraZeneca; Honoraria (self), Honoraria: Novartis; Honoraria (self): MSD; Honoraria (self): Tesaro; Honoraria (self): Lilly; Travel/Accommodation/Expenses, Travel Expenses: Pfizer; Research grant/Funding (self), Medical writing grant: Roche. P. Wimberger: Honoraria (self): Amgen; Honoraria (self): AstraZeneca; Honoraria (self): MSD; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self): PharmaMar; Honoraria (self): Eisai; Honoraria (self): Teva; Honoraria (self): Clovis; Honoraria (self): Tesaro. S. Seiler: Research grant/Funding (institution), GeparOla study was supported by AstraZeneca: AstraZeneca; Advisory/Consultancy, Advisory Boards: Amgen; Advisory/Consultancy, Advisory Boards: Hexal; Speaker Bureau/Expert testimony, Presentations: Roche; Honoraria (self), Advisory Boards: Mundipharma; Travel/Accommodation/Expenses, Travel costs: Novartis. J. Huober: Honoraria (self), Travel/Accommodation/Expenses, Travel expenses: Pfizer; Honoraria (self), Travel/Accommodation/Expenses, Travel expenses: Roche; Honoraria (self): Lilly; Honoraria (self): Celgene; Honoraria (self), Travel/Accommodation/Expenses, Travel expenses: AstraZeneca; Honoraria (self): MSD; Honoraria (self): AbbVie; Honoraria (self): Eisai; Research grant/Funding (institution): Hexal; Research grant/Funding (institution): Celgene; Honoraria (self), Research grant/Funding (institution): Novartis; Travel/Accommodation/Expenses, Travel expenses: Daiichi. W.D. Schmitt: Research grant/Funding (institution): German Breast Group; Honoraria (self): AstraZeneca. C. Jackisch: Honoraria (self): AstraZeneca; Honoraria (self): Roche. K.E. Rhiem: Honoraria (self): AstraZeneca; Honoraria (self): Tesaro; Honoraria (self): Pfizer. C. Hanusch: Honoraria (self): Roche; Honoraria (self): Novartis; Honoraria (self): Pfizer; Honoraria (self): AstraZeneca; Honoraria (self): Lilly; Honoraria (self): Celgene. C. Denkert: Honoraria (self): Novartis; Honoraria (self): Roche; Honoraria (self): MSD Oncology; Honoraria (self): Daiichi Sankyo; Research grant/Funding (institution): Myriad Genetics; Shareholder/Stockholder/Stock options, Cofounder and shareholder: Sividon Diagnostics / Myriad; Licensing/Royalties, cancer immunotherapy: EP18209672; Licensing/Royalties, therapy response: EP20150702464; Licensing/Royalties, Ki67 evaluator: Software (VMscope digital pathology). S. Loibl: Honoraria (institution), Research grant/Funding (institution), honorario for lectures and ad boards paid to institute: Amgen; Honoraria (institution), Research grant/Funding (institution), honorario for lectures and ad boards paid to institute: AbbVie; Honoraria (institution), Research grant/Funding (institution), honorario for lectures and ad boards paid to institute: AstraZeneca; Honoraria (institution), Research grant/Funding (institution), honorario for lectures and ad boards paid to institute: Celgene; Honoraria (institution), Research grant/Funding (institution), honorario for lectures and ad boards paid to institute: Novartis; Honoraria (institution), Research grant/Funding (institution), honorario for lectures and ad boards paid to institute: Pfizer; Honoraria (institution), Research grant/Funding (institution), honorario for lectures and ad boards paid to institute: Roche; Honoraria (institution), honorario for lectures and ad boards paid to institute: Seattle Genetics; Honoraria (self), honorario for lectures and ad boards paid to institute: PriME/ Medscape; Speaker Bureau/Expert testimony, lecture: Chugai; Research grant/Funding (institution): Teva; Research grant/Funding (institution): Vifor; Research grant/Funding (institution), honorarioumpaid to institute: Daiichi Sankyo; Honoraria (institution), honorarium for ad boards paid to institute: Lilly; Honoraria (institution), honorarium for ad boards paid to institute: Samsung; Advisory/Consultancy, Advisor paid to institute: Eirgenix; Advisory/Consultancy, advisor honorarium paid to institute: BMS; Advisory/Consultancy, advisor honorarium paid to institute: Puma; Honoraria (institution), honorarium paid to insitute: MSD; Research grant/Funding (institution), paid to institue: Immunomedics; Licensing/Royalties, Immunsignature in TNBC: EP14153692.0 pending. All other authors have declared no conflicts of interest.