214MO - Sacituzumab govitecan (SG) efficacy in hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2–) metastatic breast cancer (MBC) by HER2 immunohistochemistry (IHC) status in the phase III TROPiCS-02 study

Background

Tumors with HER2 IHC1+ or IHC2+ combined with a negative in situ hybridization (ISH) test are described as HER2-Low. SG, a novel Trop-2–directed antibody-drug conjugate, is approved for patients (pts) with metastatic triple-negative breast cancer in the second-line or greater setting. In the TROPiCS-02 study, SG demonstrated a 34% reduction in risk of progression or death vs treatment of physician’s choice (TPC) in heavily pretreated, endocrine-resistant HR+/HER2– MBC (Rugo H, et al. ASCO 2022; LBA1001). In this TROPiCS-02 post hoc analysis, we describe SG efficacy in HER2 IHC0 and HER2-Low HR+/HER2– MBC.

Methods

Pts with HR+/HER2– unresectable locally advanced or MBC and 2-4 prior chemotherapy regimens for MBC were randomized 1:1 to receive SG (10 mg/kg IV on d 1 and 8, every 21 d) or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine) until unacceptable toxicity or disease progression. Primary endpoint was progression-free survival (PFS) per RECIST 1.1 by central review. Pts with known HER2-positive disease were ineligible, with HER2 status (IHC and ISH) assessed locally. Table: 214MO

ISH, in situ hybridization; IHC, immunohistochemistry; mPFS, median progression-free survival; ORR, objective response rate; pts, patients; SG, sacituzumab govitecan; TPC, treatment of physician’s choice.*39 of 117 IHC2+ pts (33%; 14% of all HER2-Low pts) did not have an ISH test result but were assumed to be ISH-negative due to study eligibility criteria (HER2− disease). Similar results were observed when the 39 pts were excluded from the analysis.

Results

In the intent-to-treat (ITT) population and in each treatment arm, 92% of pts were HER2 IHC0 or HER2-Low. Baseline characteristics between HER2 IHC0 and HER2-Low were comparable and similar to that of the ITT population. Median PFS was improved with SG vs TPC in the HER2 IHC0 and HER2-Low groups (HR 0.72, P=0.05 and 0.58, P<0.001, respectively; Table). The safety profile of the subgroups was consistent with that of the overall safety population.

Conclusions

Clinical benefit with SG vs TPC in HER2 IHC0 and HER2-Low HR+/HER2- MBC was consistent with that of the TROPiCS-02 ITT population. SG should be considered an effective treatment option for pts with HR+/HER2- MBC, regardless of HER2 status.

Clinical trial identification

NCT03901339.

Editorial acknowledgement

Legal entity responsible for the study

Gilead Sciences, Inc.

Funding

Gilead Sciences, Inc.

Disclosure

P. Schmid: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Pfizer, Puma, Roche, Daiichi Sankyo, Eisai; Financial Interests, Institutional, Research Grant: Astellas, AstraZeneca, Genentech, Novartis, Oncogenex, Roche, Medivation; Other, Other, Spouse - Employee: Roche. 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, 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, Other, Travel cost and expenses: Roche, Novartis, Eisai, Daiichi Sankyo. F. Marmé: Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK/Tesaro, Clovis, Pfizer, Lilly; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Novartis, Roche, Gilead/immunomedics, EISAI, PharmaMar, GenomicHealth, Myriad, Seagen; Financial Interests, Institutional, Invited Speaker: Roche, AstraZeneca, Novartis, Roche, Eisai, Gilead/Immunomedics, MSD, German Breast Group, AGO Research GmbH, Vaccibody, GSK; Financial Interests, Institutional, Funding: AstraZeneca. H.S. Rugo: Financial Interests, Personal, Invited Speaker: PUMA, mylan; Financial Interests, Personal, Advisory Board: samsung; Financial Interests, Institutional, Invited Speaker: Novartis, Lilly, Pfizer, OBI Pharma, Immunomedics, Macrogenics, Daiichi, AstraZeneca, Roche, Merck, Odonate, sermonix, seattle genetics, polyphor, Boehringer Ingelheim; Non-Financial Interests, Advisory Role, I advise a number of companies without compensation: various. S.M. Tolaney: Financial Interests, Personal, Advisory Board, Ad Board Participant/Consultant: AstraZeneca, Eli Lilly; Financial Interests, Personal, Advisory Board, Ad board participant/Consultant: Pfizer; Financial Interests, Personal, Advisory Board, Ad board participant/consultant: Novartis, Gilead, Genentech/Roche, Eisai, Sanofi, SeaGen, Daichii Sankyo, 4D Pharma, Puma, ARC Therapeutics; Financial Interests, Personal, Advisory Board, Ad Board participant/consultant: Merck; Financial Interests, Personal, Other, Consultant: Nektar, Nanostring, Athenex, Blueprint Medicines; Financial Interests, Personal, Advisory Board, Ad board participant: Bristol-Myers Squibb, OncoPep, OncoSec, Certara, Mersana Therapeutics, Ellipses Pharma; Financial Interests, Personal, Advisory Board, Ad board participant/consultant/DSMC: Odonate; Financial Interests, Personal, Other, Steering Committee Member/Consultant: CytomX; Financial Interests, Personal, Invited Speaker, Invited speaker for pharma supported educational activity: Chugai Pharmaceuticals; Financial Interests, Personal, Advisory Board, Advisory board participant: G1 Therapeutics; Financial Interests, Personal, Advisory Board, Advisory Board Participation: Zymeworks; Financial Interests, Personal, Advisory Board, Advisory Board participation: Zentalis, OncXerna; Financial Interests, Personal, Advisory Board, Advisory board participation: Reveal Genomics; Financial Interests, Institutional, Funding: AstraZeneca, Eli Lilly, Pfizer, Sanofi, SeaGen, Odonate, Cyclacel, Exelixis, Gilead, Bristol Myers Squibb, Eisai, Merck, Novartis, Nektar, Genentech/Roche; Financial Interests, Personal and Institutional, Invited Speaker: CytomX. M. Oliveira: Financial Interests, Personal, Advisory Board: Roche, GSK, PUMA Biotechnology, AstraZeneca; Financial Interests, Personal, Invited Speaker: Roche, Seattle Genetics, Novartis, MSD, Guardant Health, Pfizer, AstraZeneca, AstraZeneca; Financial Interests, Institutional, Invited Speaker: Roche, AstraZeneca, Genentech, Novartis, Immunomedics, Seattle Genetics, GSK, Boehringer-Ingelheim, Zenith Epigenetics; Financial Interests, Invited Speaker: Roche; Non-Financial Interests, Invited Speaker: SOLTI Breast Cancer Research. D. Loirat: Financial Interests, Personal, Other, honoraria: AstraZeneca, Novartis, MSD, Lilly, Amgen, EISAI, Gilead Sciences Inc.; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Pfizer, Novartis, MSD, Immunomedics, Pharma4D, Daiichi Sankyo, Lilly, Amgen, EISAI; Financial Interests, Personal, Other, travel, accommodations, expenses: Roche, AstraZeneca, Pfizer, Novartis, Gilead Sciences Inc., Amgen. O.K. Yoon: Financial Interests, Personal, Full or part-time Employment, employee, stock options: Gilead Sciences Inc. M. Motwani: Financial Interests, Personal, Full or part-time Employment: Gilead Sciences Inc.; Financial Interests, Personal, Stocks/Shares: Gilead Sciences Inc. H. Wang: Financial Interests, Personal, Full or part-time Employment, Study Biostatistician: Gilead Sciences Inc.; Financial Interests, Personal, Stocks/Shares: Gilead Sciences Inc.; Non-Financial Interests, Institutional, Advisory Board, data safety monitoring board: Gilead Sciences Inc. R.J. Delaney: Financial Interests, Personal, Full or part-time Employment, employee: Gilead Sciences Inc. A. Bardia: Financial Interests, Institutional, Research Grant: Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health/Menarini, Immunomedics, Gilead, Daiichi Pharma, AstraZeneca, Eli Lilly; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Board: Novartis, Genentech, Merck, Radius Health/Menarini, Immunomedics, Gilead, Sanofi, Daiichi Pharma, AstraZeneca, Phillips, Eli Lilly, Foundation Medicine. All other authors have declared no conflicts of interest.