48 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 3 TROPiCS-02 Study

TABLE. SG Improved PFS vs TPC in HER2-Low and HER2 IHC0 Groups, Consistent With Outcomes in the ITT Population

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. 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 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.

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). Subgroup safety profiles were 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.

AFFILIATIONS:

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.