150P - Validation of a genomic assay in early-stage HER2+ breast cancer (BC) treated with trastuzumab and pertuzumab (HP): A correlative analysis from PHERGain phase II trial

Background

HER2DX is a prognostic (risk-score) and predictive (pathological complete response [pCR]-score) genomic assay in early-stage HER2+ BC. Here, we evaluated the ability of HER2DX following (neo)adjuvant HP-based therapy.

Methods

HER2DX was evaluated on baseline FFPE tumors from PHERGain (NCT03161353). Patients (pts) with newly diagnosed stage I-IIIA HER2+ BC and PET evaluable lesions were randomized (1:4) to receive either docetaxel (T), carboplatin (C), and HP (group A) or HP ± endocrine therapy (ET) (group B). PET was performed prior to randomization and after 2 cycles. Group A received TCHPx6 regardless of on treatment PET response. Group B received HP ± ETx2 and PET-responder (RX) pts continued with HP ± ETx6, while PET-non-RX pts received TCHPx6. After surgery, PET-RX without a pCR received TCHPx6. All pts completed HPx18. Primary objective was the association of HER2DX with pCR (ypT0/is ypN0). Secondary objective was the association of HER2DX risk-score with invasive disease-free survival (iDFS).

Results

HER2DX was evaluated in 292 (82.0%) pts. Clinical T2-4 and node-negative disease represented 84.6% and 49.3%, respectively, and 66.4% of tumors were hormone receptor (HR) positive. The overall pCR rate was 38.0% (56.4% in group A and 33.8% in group B). In the multivariable analysis, HER2DX pCR-score (as a continuous variable) was significantly associated with pCR (odds ratio [OR] per 10-unit increase=1.29 (1.5-1.8), p<0.001), after adjusting for treatment and clinicopathological factors such as HR status, treatment group, or PET response. In the overall population, the pCR rates in HER2DX pCR-high, med, and low groups were 50.4%, 35.8%, and 23.2% (pCR-high vs pCR-low OR=3.37, p<0.001), respectively. HER2DX low-risk showed a numerically better 3-year iDFS than HER2DX high-risk pts (100% vs 93.5%; hazard ratio= 0.37 [0.1-1.7]) after adjusting by pCR status. Eight out of 9 pts with metastatic progression had HER2DX high-risk prognostic score.

Conclusions

HER2DX predicts pCR following neoadjuvant HP-based therapy (with or without chemotherapy) and identifies pts with a higher risk of recurrence. This assay might help individualize HP-based therapy in early HER2+ BC.

Clinical trial identification

NCT03161353.

Editorial acknowledgement

Legal entity responsible for the study

MEDSIR.

Funding

Reveal Genomics, MEDSIR.

Disclosure

L. Pare Brunet: Financial Interests, Institutional, Full or part-time Employment: Reveal Genomics S.L.; Financial Interests, Institutional, Other, Patent pending: In vitro method for the prognosis of patients suffering from HER2-positive breast cancer - 905333: Reveal Genomics S.L. G. Villacampa Javierre: Financial Interests, Personal, Invited Speaker, Invited speaker in a course: MSD; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker, Invited speaker in an internal training: Pierre Fabrer, GSK; Financial Interests, Personal, Invited Speaker, Internal discussion about the interpretation of some published results: Pfizer; Financial Interests, Personal, Other, Collaborations with specific projects: Reveal Genomics. F. Brasó-Maristany: Financial Interests, Personal, Advisory Board: Reveal Genomics. M. Gion Cortes: Financial Interests, Personal, Invited Speaker: Roche, Daiichi Sankyo, Novartis; Financial Interests, Personal, Other, Travel expenses: Roche, Pfizer; Financial Interests, Personal, Advisory Board: Gilead; Financial Interests, Personal, Full or part-time Employment: MEDSIR. P. Schmid: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Pfizer, Puma, Roche, Gilead, Eisai, MSD, Seagen, Amgen, Celgene, Lilly; Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Genentech, Novartis, Oncogenex, Roche, Medivation. M.A. Colleoni: Financial Interests, Institutional, Research Grant: Roche; Non-Financial Interests, Leadership Role, CO-Chair Scientific Committee: International Breast Cancer Study Group. P. Galván: Financial Interests, Personal, Full or part-time Employment: Reveal Genomics. J. Parker: Financial Interests, Personal, Other, Advisory: Reveal Genomics, Bristol Myers Squibb; Financial Interests, Personal, Full or part-time Employment: LifeEdit Therapeutics; Financial Interests, Personal, Ownership Interest: Reveal Genomics, GeneCentric; Financial Interests, Personal, Royalties: Veracyte. C.M. Perou: Financial Interests, Personal, Member of Board of Directors: GeneCentric Therapeutics; Financial Interests, Personal, Stocks/Shares: GeneCentric Therapeutics, Bioclassifier LLC, Reveal Genomics; Financial Interests, Personal, Royalties, from PAM50 licensing: Bioclassifier LLC; Financial Interests, Personal, Royalties: GeneCentric Therapeutics; Non-Financial Interests, Advisory Role: GeneCentric Therapeutics, Bioclassifier LLC, Reveal Genomics. P. Villagrasa Gonzalez: Financial Interests, Personal, Full or part-time Employment, CEO and co-founder of the company: Reveal Genomics S.L.; Financial Interests, Personal, Ownership Interest: Reveal Genomics S.L.; Financial Interests, Personal, Royalties, PCT/EP2021/086493 - In Vitro method for the prognosis of patients suffering from HER2-positive breast cancer: Reveal Genomics S.L. A. Prat: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker, Lecture fees: Novartis, Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Novartis, Pfizer, Oncolytics Biotech, Guardant Health, Peptomyc; Financial Interests, Institutional, Invited Speaker, Clinical trials: Daiichi Sankyo; Financial Interests, Institutional, Other, Contracted research: Boehringer Ingelheim, Medica Scientia inno. Research; Financial Interests, Personal, Advisory Board: AstraZeneca, 1TRIALSP, S.L.; Financial Interests, Personal, Member of Board of Directors, Leadership role: Reveal Genomics, SL.; Financial Interests, Personal, Stocks/Shares: Reveal Genomics, Oncolytics Biotech; Financial Interests, Personal, Royalties: Reveal Genomics, International Oncology Bureau, S.L.; Financial Interests, Institutional, Local PI: Roche, AstraZeneca; Financial Interests, Personal and Institutional, Steering Committee Member: Daiichi Sankyo; Financial Interests, Institutional, Coordinating PI: Novartis; Non-Financial Interests, Institutional, Other, Leadership roles: Patronage committee: SOLTI Foundation, Actitud Frente al Cáncer Foundation; Non-Financial Interests, Personal, Other, Asociación Española de Investigación sobre el Cáncer: ASEICA. J. Cortés: Financial Interests, Personal, Advisory Board: Roche, Celgene, Cellestia, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Merck Sharp& Dohme, GSK, Leuko, Bioasis, Clovis oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics; Financial Interests, Personal, Invited Speaker: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp & Dohme, Daiichi Sankyo; Financial Interests, Personal, Other, Consulting/advisor: Expres2ion Biotechnologies; Financial Interests, Personal, Stocks/Shares: MEDSIR, Nektar Therapeutics; Financial Interests, Institutional, Research Grant: Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer Healthcare, Eisai, Guardanth health, Merck Sharp & Dohme , Pfizer, Piqur Therapeutics, Puma B, Queen Mary University of London; Other, Travel cost and expenses: Roche, Novartis, Eisai, Daiichi Sankyo, Pfizer, Gilead, AstraZeneca. All other authors have declared no conflicts of interest.