394P - Quantitative standardized high sensitivity (HS)-HER2 testing predicts outcomes with trastuzumab deruxtecan (T-DXd) for metastatic breast cancer (MBC)

Background

T-DXd is currently approved for the treatment of HER2+ and HER2-low MBC. Immunohistochemistry (IHC) for HER2 does not reliably predict outcomes within these groups. We assessed the performance of a new quantitative test to predict outcomes with T-DXd for MBC.

Methods

We retrieved samples for patients (pts) with MBC receiving T-DXd at DFCI from 7/2017 to 2/2023. The QuPath Qymia method of quantitative immunofluorescence was used to determine HS-HER2. A pathologist circled the region within each biopsy to be measured; then, using a cell line standard curve calibrated by mass spectrometry, the amount of HER2 protein was measured in units of attomols/mmˆ2 in pre-T-DXd samples. We evaluated the association of HS-HER2 in the closest samples collected prior to T-DXd with time to next treatment (TTNT) and overall survival (OS) in continuous terms and by quartiles of HS-HER2.

Results

Samples from 51 pts (32 with HER2+, 19 with HER2- MBC at time of T-DXd) were analyzed with HS-HER2; the primary tumor in 20 pts (39.2%), metastatic biopsy in 13 (25.5%), and both in 18 (35.3%). The median time from tissue collection to T-DXd was 31.3 months (range 2.5 – 204). Across all pts, HS-HER2 was found to be associated with TTNT (hazard ratio [HR] per 5-unit increment 0.78, p75% 11.67 5.83-NA 0.17 0.07-0.44

Conclusions

The quantitative assessment of HER2 in attomols/mmˆ2 was found to predict clinical outcomes with T-DXd for MBC, including in subgroup analyses for HER2+ and HER2- MBC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

P. Tarantino: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche; Financial Interests, Personal, Advisory Board: Daiichi Sankyo, AstraZeneca, Daiichi Sankyo, Genentech, Eli Lilly, Gilead; Financial Interests, Institutional, Funding: AstraZeneca. L. Alder: Financial Interests, Research Funding, clinical trial funding: BergenBio, ORIC. C. Anders: Financial Interests, Research Funding: PUMA, Lilly, Merck, Seattle Genetics, Nektar, Tesaro, G1-Therapeutics, ZION, Novartis, Pfizer, AstraZeneca, Elucida, Caris, Incyclix; Financial Interests, Speaker, Consultant, Advisor, consulting: Genentech, Eisai, IPSEN, Seattle Genetics, AstraZeneca, Novartis, Immunomedics, Elucida, Athenex, Roche; Financial Interests, Royalties: UpToDate, Jones and Bartlett. S. Morganti: Other, expenses: AstraZeneca, Menarini. A.C. Garrido-Castro: Financial Interests, Personal, Advisory Board: AstraZeneca, Daiichi Sankyo, Novartis; Financial Interests, Personal, Invited Speaker: AstraZeneca, Daiichi Sankyo; Financial Interests, Institutional, Funding, Research funding: AstraZeneca, Daiichi Sankyo, Gilead Sciences, Merck, Zenith Epigenetics, Bristol-Myers Squibb, Novartis, Biovica, Foundation Medicine, 4D Path, Precede Biosciences; Other support (travel, accommodations, expenses): Roche/Genentech, Gilead Sciences, AstraZeneca, Daiichi Sankyo, Novartis, Merck. P. Lorusso: Financial Interests, Advisory Board: AbbVie, Takeda, Agenus, IQVIA, Pfizer, GSK, QED Therapeutics, AstraZeneca, EMD Serono, Kyowa Kirin Pharmaceutical Development, Kineta, Inc., Zentalis Pharmaceuticals, Molecular Templates, ABL Bio, STCube Pharmaceuticals, I-Mab, Seagen, imCheck, Relay Therapeutics, Stemline, Compass BADX, Mekanistic, Mersana Therapeutics, BAKX Therapeutics, Scenic Biotech, Qualigen, NeuroTrials, Actuate Therapeutics, Atreca Development, Quanta Therapeutics, Schrodinger, Boehrigner Ingelheim; Financial Interests, Other, imCORE Alliance: Roche-Genentech; Financial Interests, Speaker, Consultant, Advisor: SOTIO, I-Mab, Roivant Sciences; Financial Interests, Other, IDMC: SOTIO; Financial Interests, Advisory Board, Data Safety Monitoring Board: Amgen CodeBreak 202. M. Lustberg: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Gilead; Financial Interests, Personal, Invited Speaker: Loxo Lilly; Financial Interests, Personal, Other, consultant: Pfizer. S. Sammons: Financial Interests, Institutional, Research Funding: AstraZeneca, Eli Lilly, Relay, SEAGEN, Sermonix; Financial Interests, Speaker, Consultant, Advisor, consulting: Foundation Medicine, AstraZeneca, Daichii Sankyo, Eli Lilly, Pfizer, Incyclix, Relay, Gilead, Sermonix, Novartis. N. Lin: Financial Interests, Research Funding: Genentech (and Zion Pharmaceutical as part of GNE), Pfizer, Merck, Seattle Genetics (now Pfizer), Olema Pharmaceuticals, AstraZeneca; Financial Interests, Speaker, Consultant, Advisor, consulting: Puma, Seattle Genetics, Daiichi Sankyo, AstraZeneca, Olema Pharmaceuticals, Janssen, Blueprint Medicines, Stemline/Menarini, Artera Inc., Eisai; Financial Interests, Royalties: UpToDate; Financial Interests, Other, travel support: Olema Pharmaceuticals. D. Rimm: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Cell Signaling Technology, Cepheid, Danaher, Daiichi Sankyo, Merck, Monopteros, Nanostring, PAIGE.AI, Regeneron, Ventana; Financial Interests, Personal, Speaker, Consultant, Advisor, consultant: Halda Bio, Immunogen, Incendia, NextCure, Sanofi, Verily; Financial Interests, Personal and Institutional, Research Funding: Amgen, Cepheid, Navigate BioPharma, NextCure, Konica/Minolta, Akoya; Financial Interests, Personal, Royalties: Rarecyte. S.M. Tolaney: Financial Interests, Research Funding: Genentech/Roche, Merck, Exelixis, Pfizer, Lilly, Novartis, Bristol Myers Squibb, Eisai, AstraZeneca, Gilead, NanoString Technologies, Seattle Genetics, OncoPep; Financial Interests, Speaker, Consultant, Advisor: Novartis, Pfizer (Seagen), Merck, Eli Lilly, AstraZeneca, Genentech/Roche, Eisai, Sanofi, Bristol Myers Squibb, CytomX Therapeutics, Daiichi Sankyo, Gilead, Zymeworks, Zentalis, Blueprint Medicines, Reveal Genomics, Sumitovant Biopharma, Umoja Biopharma, Artios Pharma, Menarini/Stemline, Aadi Bio, Bayer, Incyte Corp, Jazz Pharmaceuticals, Natera, Tango Therapeutics, Systimmune, eFFECTOR, Hengrui USA, Cullinan Oncology, Circle Pharma, Arvinas; Financial Interests, Other, travel support: Eli Lilly, Sanofi, Gilead, Jazz Pharma. All other authors have declared no conflicts of interest.