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. In this TROPiCS-02 post hoc analysis, we describe SG efficacy in HER2 IHC0 and HER2-low HR+/HER2– mBC.
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 d1 and d8, every 21d) or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine) until unacceptable toxicity or disease progression. Primary end point 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.
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). Subgroup safety profiles were consistent with that of the overall safety population.
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.
Sara M. Tolaney,1 Peter Schmid,2 Javier Cortes,3 Frederik Marmé,4 Hope S. Rugo,5 Mafalda Oliveira,6 Delphine Loirat,7 Komal Jhaveri,8 Oh Kyu Yoon,9 Monica Motwani,9 Hao Wang,9 Rosemary Delaney,10 Aditya Bardia11
1Dana-Farber Cancer Institute, Boston, MA.
2Barts Cancer Institute, Queen Mary University of London, London, United Kingdom.
3International Breast Cancer Center (IBCC), Quiron Group, Madrid and Barcelona, Spain.
4Heidelberg University, University Hospital Mannheim, Heidelberg, Germany.
5University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA.
6Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology, Barcelona, Spain.
7Institut Curie, Paris, France.
8Memorial Sloan Kettering Cancer Center, New York, NY.
9Gilead Sciences, Inc, Foster City, CA.
10Gilead Sciences, Inc, Morris Plains, NJ.
11Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA.