237MO - TNBC-DX genomic test in early-stage triple-negative breast cancer treated with neoadjuvant taxane-based therapy without immunotherapy

Background

There is an urgent need for biomarkers to tailor treatment strategies in early-stage triple-negative breast cancer (eTNBC). Here, we developed and validated the TNBC-DX genomic test.

Methods

Firstly, we utilized the original HER2DX assay developed for HER2+ breast cancer as a starting point to evaluate the potential for improving the model using information from the SCAN-B, CALGB-40603, and BrighTNess trials (n=1,120). Secondly, the TNBC-DX was defined (pCR and risk scores) both as a continuous score and group categories using pre-defined cut-off. Thirdly, the model was externally validated in 418 patients with stage 1-3 eTNBC undergoing neoadjuvant taxane-based chemotherapy without anthracycline/cyclophosphamide and pembrolizumab from 2 external cohorts: i) WSG-ADAPT-TN phase II study (NCT01815242) and ii) MMJ-CAR-2014-01 study (NCT01560663). The primary objective of the study was to evaluate the association between TNBC-DX and efficacy outcomes (pCR, distant disease-free survival [DDFS] and overall survival [OS]) in the external validation cohorts. Logistic regression models, both uni- and multivariable, along with Cox models, were used to quantify these associations.

Results

The TNBC-DX genomic test was created incorporating tumor size, nodal staging, and 2 gene signatures (10-gene core immune gene, and 4-gene tumor cell proliferation). The TNBC-DX pCR score as a continuous score was significantly associated with pCR rates in both studies individually (p<0.01). The combined pCR rates for the TNBC-DX pCR-high, -medium, and -low categories were 57.2%, 43.9%, and 16.7% respectively (odds ratio for pCR-high vs pCR-low=6.69, p<0.001). Additionally, the TNBC-DX risk score was significantly associated with DDFS (hazard ratio [HR] for risk-high vs risk-low=3.06, p<0.001) and with OS (HR=3.11, p<0.001). The association remained statistically significant after accounting for pCR status.

Conclusions

TNBC-DX genomic test predicts response to neoadjuvant taxane-carboplatin chemotherapy in eTNBC, and helps forecast the patient´s long-term survival in the absence of neoadjuvant anthracycline, cyclophosphamide, and immunotherapy.

Clinical trial identification

NCT01815242 and NCT01560663.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Reveal Genomics.

Disclosure

M. Martin Jimenez: Financial Interests, Personal, Advisory Board: AstraZeneca, Lilly, Roche/Genentech, Daiichi Sankyo, Menarinio-Stemline; Financial Interests, Personal, Invited Speaker: Pfizer, AstraZeneca, Lilly, Novartis, Roche/Genentech; Financial Interests, Institutional, Research Grant: Novartis, Roche, Puma; Non-Financial Interests, Member of Board of Directors: Trio; Non-Financial Interests, Leadership Role: GEICAM; Non-Financial Interests, Member: ASCO; Non-Financial Interests, Advisory Board: SEOM. O. Gluz: Financial Interests, Personal, Advisory Board: Roche, Lilly, Novartis, Pierre Fabre, MSD, Pfizer, Gilead, Seagen, Agendia; Financial Interests, Personal, Invited Speaker: AstraZeneca, Exact Science; Financial Interests, Institutional, Coordinating PI: Roche, LIlly; Non-Financial Interests, Leadership Role: West German Study Group; Non-Financial Interests, Personal, Proprietary Information: West German Study Group. G. Villacampa: 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. S. Lopez-Tarruella Cobo: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Pfizer, Novartis, Lilly, Gilead, GSK, Roche, Pierre Fabre, Seagen, Menarini_Stemline, Gebro Pharma, Veracyte, MSD; Financial Interests, Personal, Invited Speaker: Lilly; Non-Financial Interests, Member of Board of Directors: GEICAM, SEOM. F. Brasó-Maristany: Financial Interests, Personal, Full or part-time Employment, part time employment: Reveal Genomics SL; Financial Interests, Personal, Other, Patents filed: EP23382703 and EP23383369.: Reveal Genomics SL; Financial Interests, Personal, Other, Patents filed: PCT/EP2022/086493, PCT/EP2023/060810: Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer. Y. Jerez Gilarranz: Financial Interests, Personal, Invited Speaker: Daichii, Novartis, roche, pfizer. S. Kummel: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Celgene, Daiichi Sankyo, Lilly, MSD, Novartis, Seagen, Pfizer, Pfizer, Roche, Somatex, Gilead, Sanofi, Hologic, PINK; Financial Interests, Personal, Invited Speaker: ExactScience, MSD, Lilly, Gilead, Roche, Sanofi, Daiichi Sankyo; Financial Interests, Personal, Ownership Interest, Minority Ownership: WSG Study Group; Financial Interests, Personal and Institutional, Coordinating PI: Roche, Novartis; Financial Interests, Institutional, Local PI: Roche, Novartis, Lilly, Somatex, AstraZeneca, MSD. B. Conte: Financial Interests, Personal, Speaker’s Bureau: Veracyte ; Financial Interests, Personal, Other: Medsite, Novartis. I. Echavarria Diaz-Guardamino: Financial Interests, Personal, Invited Speaker: Pfizer, Novartis, AstraZeneca, Pierre Fabre, Lilly, Gilead; Financial Interests, Personal, Advisory Board: Daichi Sankyo, Lilly. B. Herrero Lopez: Financial Interests, Personal, Invited Speaker: Roche, Novartis, Pharmamar, Eisai, AstraZeneca, Daichii Sankyo, Pfizer, Teva, Kiowa Kirin, GSK, Gilead. C.M. Perou: Financial Interests, Personal, Other, consultant: GeneCentric Therapeutics, Bioclassifier LLC, Reveal Genomics; Financial Interests, Personal, Member of Board of Directors: GeneCentric Therapeutics; Financial Interests, Personal, Ownership Interest: GeneCentric Therapeutics, Bioclassifier LLC, Reveal Genomics; Financial Interests, Personal, Royalties: Bioclassifier LLC. 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: SOLTI; Financial Interests, Institutional, Other, Patent filed: EP23382703: Reveal Genomics S.L.; Financial Interests, Institutional, Other, Patent filed: EP23383369: 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, Peptomyc; Financial Interests, Institutional, Invited Speaker, Clinical trials: Daiichi Sankyo; Financial Interests, Institutional, Other, Contracted research: Boehringer, Medica Scientia inno. Research; Financial Interests, Personal, Advisory Board: AstraZeneca, Reveal Genomics, 1TRIALSP, S.L.; Financial Interests, Personal, Member of Board of Directors, Leadership role: Reveal Genomics, SL.; Financial Interests, Personal, Stocks/Shares: Reveal Genomics; 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; Financial Interests, Institutional, Funding: Reveal Genomics; Non-Financial Interests, Institutional, Other, Leadership roles: Patronage committee: Actitud Frente al Cáncer Foundation; Non-Financial Interests, Personal, Other, Asociación Española de Investigación sobre el Cáncer: ASEICA; Non-Financial Interests, Personal, Other, Research Foundation that gives grants to researchers: FERO. N. Harbeck: Financial Interests, Personal, Invited Speaker: AstraZeneca, Daiichi Sankyo, Lilly, MSD, Novartis, Pierre Fabre, Roche, Seagen, Art Tempi, Onkowissen, Medscape, Gilead, Sanofi, Zuelligpharma, Viatris; Financial Interests, Personal, Other, IDMC: Roche; Financial Interests, Personal, Advisory Board: Sandoz-Hexal, Seagen, Aptitude Health, Pfizer, Gilead, Sanofi; Financial Interests, Personal, Other, Husband: WSG (Husband); Financial Interests, Personal, Ownership Interest: West German Study Group; Financial Interests, Institutional, Coordinating PI: AstraZeneca; Financial Interests, Institutional, Funding: BMS, Daiichi Sankyo, MSD, Roche, Seagen, TRIO, WSG, Gilead; Financial Interests, Institutional, Steering Committee Member: Lilly, Pierre Fabre; Non-Financial Interests, Member, Member German AGO Breast Guideline Committee: AGO Breast Committee; Non-Financial Interests, Member, Breast Cancer Educational Programs: ESO/ESCO; Other, Founding Editor: BreastCare Journal. All other authors have declared no conflicts of interest.