Abstract 194P
Background
SG is a Trop-2–directed antibody-drug conjugate approved for metastatic triple-negative BC in multiple countries and pretreated HR+/HER2– mBC in the US. In TROPiCS-02, SG significantly improved progression-free survival (PFS; median, 5.5 vs 4.0 mo; HR, 0.66; P=0.0003) and overall survival (OS; median, 14.4 vs 11.2 mo; HR, 0.79; P=0.020) vs treatment of physician’s choice (TPC) in patients (pts) with pretreated, endocrine-resistant HR+/HER2– mBC, with a manageable safety profile (Rugo et al. ESMO 2022). In the ASCENT study, UGT1A1 polymorphisms were associated with neutropenia, anemia, and diarrhea in SG-treated pts (Rugo et al. npj Breast Cancer 2022). Here, we report TROPiCS-02 safety analyses by UGT1A1 status.
Methods
Pts with HR+/HER2– mBC who received prior taxane, endocrine therapy, CDK4/6 inhibitor, and 2-4 prior chemotherapies (CT) were randomized 1:1 to SG or TPC. The primary endpoint was PFS by central review per RECIST 1.1; secondary endpoints included OS and safety. A post-hoc safety analysis was performed by UGT1A1 status.
Results
Of 543 enrolled pts (median number of prior CT for mBC, 3; visceral metastases, 95%), 517 (SG, n=268; TPC, n=249) received ≥1 dose of study treatment. UGT1A1 status in SG pts was: *1/*1 (n=104; 38%; wild type), *1/*28 (n=119; 44%), and *28/*28 (n=25; 9%); the respective median relative dose intensity was 99%, 98% and 94%. In SG pts, grade ≥3 treatment-emergent adverse events (TEAEs) included neutropenia (52%), diarrhea (10%), anemia (8%), and febrile neutropenia (6%). In pts with UGT1A1 *1/*1, *1/*28, and *28/*28 genotypes, grade ≥3 TEAEs for SG included: neutropenia (45%, 57%, and 64%), diarrhea (6%, 13%, and 24%), anemia (6%, 8%, and 8%), and febrile neutropenia (6%, 7%, and 4%), respectively. Myeloid growth factors (initiated on/after first dose) were used to manage neutropenia in 54% of pts in the SG group (33%, *1/*1; 49%, *1/*28; 11%, *28/*28). TEAEs were managed similarly regardless of UGT1A1 status.
Conclusions
SG had a manageable safety profile consistent with previous reports and across UGT1A1 status. UGT1A1 testing is not required for SG use in pretreated, endocrine-resistant HR+/HER2– mBC.
Clinical trial identification
NCT03901339.
Legal entity responsible for the study
Gilead Sciences, Inc.
Funding
Gilead Sciences, Inc.
Disclosure
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: Seagen, Daiichi Sankyo, GSK, AstraZeneca, Roche, AstraZeneca, Novartis, Roche, Eisai, Gilead/Immunomedics, MSD, German Breast Group, AGO Research GmbH, Vaccibody, GSK; Financial Interests, Institutional, Advisory Board: Roche, Immunicom; Financial Interests, Institutional, Funding: AstraZeneca, Lilly, Seagen. H.S. Rugo: Financial Interests, Personal, Funding: Puma Biotechnology, Mylan, Samsung Bioepis; Financial Interests, Institutional, Funding: Macrogenics, OBI Pharma, Pfizer, Novartis, Lilly, Genentech, Merck, Odonate Therapeutics, Daiichi Sankyo, Seattle Genetics, Sermonix Pharmaceuticals, AstraZeneca, Gilead Sciences, Ayala Pharmaceuticals. 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, Daiichi Sankyo, 4D Pharma, ARC Therapeutics; Financial Interests, Personal, Advisory Board, Ad Board participant/consultant: Merck; Financial Interests, Personal, Advisory Board, Ad board participant: Bristol Myers Squibb, Mersana Therapeutics, Ellipses Pharma; Financial Interests, Personal, Other, Steering Committee Member/Consultant: CytomX; Financial Interests, Personal, Other, Consultant: Blueprint Medicines; Financial Interests, Personal, Advisory Board, Advisory Board Participation: Zymeworks; Financial Interests, Personal, Advisory Board, Advisory Board participation: Zentalis, OncXerna, Myovant, Bayer, Zetagen, Infinity Therapeutics, Umoja Biopharma; Financial Interests, Personal, Advisory Board, Advisory board participation: Reveal Genomics; Financial Interests, Personal, Advisory Board, Advisory Board participation/consulting: Menarini/Stemline; Financial Interests, Personal, Other, Consulting: Aadi BioPharma; 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. A. Bardia: Financial Interests, Personal, Advisory Board: Pfizer, Novartis, Genentech, Merck, Sanofi, Eisai, Lilly, Mersana, AstraZeneca/Daiichi, Menarini, Gilead; Financial Interests, Personal, Royalties: UpToDate; Financial Interests, Institutional, Invited Speaker: Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics/Gilead, Daiichi Pharma/AstraZeneca, Eli Lilly.; Non-Financial Interests, Principal Investigator: Gilead, Mersana, AstraZeneca/Daiichi, Novartis, Pfizer, Genentech, Lilly, Merck, Sanofi. 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, Spouse - Employee: Roche. W. Verret, T. Valdez, H. Wang: Financial Interests, Personal, Full or part-time Employment: Gilead Sciences, Inc.; Financial Interests, Personal, Stocks/Shares: Gilead Sciences, Inc. 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.