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Mini Oral session 2

3MO - HER2 expression and early response to patritumab deruxtecan (HER3-DXd) in early-stage hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer (BC): a correlative analysis from SOLTI-TOT-HER3 trial

Date

12 May 2023

Session

Mini Oral session 2

Topics

Tumour Site

Breast Cancer

Presenters

Fara Brasó-Maristany

Citation

Annals of Oncology (2023) 8 (1suppl_4): 101218-101218. 10.1016/esmoop/esmoop101218

Authors

F. Brasó-Maristany1, P. Tolosa Ortega2, M. Margeli Vila3, J. Cruz Jurado4, F.J. Salvador Bofill5, J.M. Cejalvo6, M.A. Arumi de Dios7, M.J. Vidal Losada8, S. Pernas Simon9, S. Esker10, P. Fan11, A. Santhanagopal10, O. Martinez Saez8, G. Villacampa12, R. Sanchez Bayona2, J.M. Ferrero Cafiero13, C. Falato14, T. Pascual15, A. Prat16

Author affiliations

  • 1 IDIBAPS - Fundació de Recerca Clinic Barcelona, Barcelona/ES
  • 2 Hospital Universitario 12 de Octubre, Madrid/ES
  • 3 ICO - Institut Català d'Oncologia Badalona (Hospital Universitario Germans Trias i Pujol), Badalona/ES
  • 4 Hospital Universitario de Canarias, San Cristobal de la Laguna/ES
  • 5 Hospital Universitario Virgen de Valme, 41013 - Seville/ES
  • 6 Hospital Clinico Universitario de Valencia, Valencia/ES
  • 7 Universitat de Barcelona - Facultat de Medicina, 8036 - Barcelona/ES
  • 8 Hospital Clinic of Barcelona, Barcelona/ES
  • 9 ICO - Institut Català d'Oncologia l'Hospitalet (Hospital Duran i Reynals), L'Hospitalet de Llobregat/ES
  • 10 Daiichi Sankyo, Inc., 07920-2311 - Basking Ridge/US
  • 11 Daiichi Sankyo, Inc., Basking Ridge/US
  • 12 SOLTI - Grupo Espanol de Estudio, 8035 - Barcelona/ES
  • 13 SOLTI HQ, Barcelona/ES
  • 14 IDIBAPS - August Pi i Sunyer Biomedical Research Institute, Barcelona/ES
  • 15 SOLTI / Hospital Clinic of Barcelona, Barcelona/ES
  • 16 Hospital Clinic y Provincial de Barcelona, Barcelona/ES

Resources

This content is available to ESMO members and event participants.

Abstract 3MO

Background

HER3-DXd and trastuzumab deruxtecan (T-DXd) are antibody-drug-conjugates (ADCs) directed against HER3 and HER2, respectively. Both drugs have shown efficacy in patients (pt) with HR+/HER2- BC. Baseline HER3 protein or mRNA levels do not predict efficacy from HER3-DXd. Here, we aimed to evaluate the association of early response to HER3-DXd with HER2 levels.

Methods

TOT-HER3 (NCT04610528), a window-of-opportunity trial, evaluated a single dose of HER3-DXd in 77 pts with untreated HR+/HER2- early BC in Part A (6.4 mg/kg) and 17 in Part B (5.6 mg/kg). Primary objective was CelTIL score [a surrogate of response that combines tumor cellularity and tumor-infiltrating lymphocytes] variation between baseline and day 21 tumor samples. Here, CelTIL response was defined as an absolute increase of 20 at day 21. HER2 expression was determined by immunohistochemistry (IHC). RNA and DNA were purified from baseline FFPE tumor samples and analyzed using the nCounter and the VHIO-300 NGS platforms, respectively. Logistic regression models and area under the ROC Curve (AUC) estimated the performance of HER2 IHC, mRNA or copy-number (CN) levels with CelTIL response.

Results

In TOT-HER3 Part A, HER2 IHC status was 32% HER2 0, 38% HER2 1+ and 30% HER2 2+. Distribution of high CelTIL responders was 40% in HER2 0, 45% in HER2 1+ and 13% in HER2 2+ (p=0.034). High ERBB2 mRNA and RNA-based HER2 amplicon signatures were significantly associated with low CelTIL response (ERBB2: Odds Ratio [OR]=0.34, p<0.001, AUC=0.71; and HER2 amplicon: OR=0.20, p=0.005, AUC=0.74). The association of ERBB2 mRNA with CelTIL response was independent of HER2 IHC expression (p=0.002), PAM50 subtype (p=0.001) or proliferation (p=0.003). High HER2 CN signal was found associated with low CelTIL response (p=0.005). The association of HER2 IHC and ERBB2 mRNA with CelTIL response will be independently validated in TOT-HER3 Part B.

Conclusions

Low HER2 IHC, mRNA or CN levels in early-stage HR+/HER2- BC are associated with high response to HER3-DXd. HER3-DXd might be highly active in HR+ BC with very low HER2 levels, thereby offering a new therapeutic paradigm to this subset of patients.

Legal entity responsible for the study

SOLTI.

Funding

Has not received any funding.

Disclosure

F. Brasó-Maristany: Financial Interests, Personal, Licensing Fees: Reveal Genomics. M. Oliveira: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo/AstraZeneca, Gilead, Pierre Fabre, Roche, Seagen, iTEOS, Relay Therapeutics; Financial Interests, Personal, Invited Speaker: Gilead, MSD, Novartis, Pfizer, Roche, Seattle Genetics, AstraZeneca; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Boehringer-Ingelheim, GSK, Roche, Seattle Genetics, Zenith Epigenetics, Gilead, Ayala Pharmaceuticals; Financial Interests, Invited Speaker: Roche; Non-Financial Interests, Invited Speaker: SOLTI Breast Cancer Research; Other, Travel Grant: Pierre Fabre, Eisai, Gilead, AstraZeneca. P. Tolosa Ortega: Financial Interests, Personal, Invited Speaker: Novartis, Pfizer, Lilly, Seagen, AstraZeneca, Daiichi Sankyo and MSD; Financial Interests, Personal, Advisory Board: Novartis, Adamed, Seagen and Daiichi Sankyo; Financial Interests, Personal, Full or part-time Employment, Medical Advisor and Madical Monitor: SOLTI. M. Margeli Vila: Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Novartis, MSD, Gilead, Lilly, Pierre Fabre; Financial Interests, Personal, Other, Travel expences: Gylead; Financial Interests, Institutional, Invited Speaker, I have received research funding for my institution from Pfizer: Pfizer. J. Cruz Jurado: Financial Interests, Personal, Advisory Board: PharmaMar, Roche, Lilly, Pfizer, Novartis, Gilead, AstraZeneca, Daiichi, Seagen, GSK, bayer; Financial Interests, Personal, Invited Speaker: PharmaMar, Roche, Lilly, Pfizer, Novartis, Eisai, Gilead, AstraZeneca, Daiichi, Seagen, Esteve, Roche. J.M. Cejalvo: Financial Interests, Institutional, Invited Speaker: Pfizer, Novartis. S. Pernas Simon: Financial Interests, Personal, Advisory Board: Seagen, AstraZeneca- Daiichi Sankyo, Pierre-Fabre, Pfizer; Financial Interests, Personal, Invited Speaker: Lilly, Novartis, Eisai, Roche; Financial Interests, Institutional, Invited Speaker: Astra-Zeneca, Novartis, Daiichi Sankyo; Non-Financial Interests, Invited Speaker: SOLTI. S. Esker: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. P. Fan: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. A. Santhanagopal: Financial Interests, Personal, Full or part-time Employment: Daiichi Sankyo. O. Martinez Saez: Financial Interests, Personal, Invited Speaker: Novartis, Eisai; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Other, Travel expenses: Roche; Financial Interests, Personal, Other, Medical advisory: Reveal Genomics. 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. R. Sanchez Bayona: Financial Interests, Personal, Invited Speaker: Novartis, Lilly Oncology, GSK Oncology, AstraZeneca, Seagen, Clovis Oncology; Financial Interests, Personal, Other, Travel and accommodation: Pfizer; Financial Interests, Personal, Full or part-time Employment, Medical Advisor: SOLTI; Financial Interests, Personal, Other, Medical Monitor in HARMONIA Trial: Novartis. T. Pascual: Financial Interests, Personal, Invited Speaker: Pfizer/ AstraZeneca / Veracyte / Novartis; Financial Interests, Personal, Advisory Board: Roche/Genentech. 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, BMS, Puma, Oncolytics Biotech, MSD, Guardant Health, 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; Financial Interests, Personal, Invited Speaker, Leadership role: Reveal Genomics, SL.; Financial Interests, Personal, Stocks/Shares: Reveal Genomics, Oncolytics Biotech; Financial Interests, Personal, Royalties: Reveal Genomics; Financial Interests, Institutional, Invited Speaker: Roche, AstraZeneca, Novartis; Financial Interests, Personal and Institutional, Invited Speaker: Daiichi Sankyo; Non-Financial Interests, Institutional, Other, Leadership roles: Patronage committee: SOLTI Foundation, Actitud Frente al Cáncer Foundation. All other authors have declared no conflicts of interest.

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