Author(s): Hope S Rugo, MD1; Aditya Bardia, MD2; Frederik Marmé, MD3; Javier Cortés, MD4,5,6; Peter Schmid, MD7; Delphine Loirat, MD8; Olivier Trédan, MD9,10; Eva Ciruelos, MD11; Florence Dalenc, MD12; Patricia Gómez Pardo, MD13; Komal L Jhaveri, MD14,15; Rosemary Delaney, MPH16; Theresa Valdez, PharmD16; Hao Wang, PhD16; Monica Motwani, PhD16; Oh Kyu Yoon, PhD16; Wendy Verret, PhD16; Sara M Tolaney, MD17
Sacituzumab govitecan demonstrated significant progression-free survival benefit over chemotherapy in the phase 3 TROPiCS-02 trial in patients with pretreated, endocrine-resistant hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+ and HER2–) metastatic breast cancer with limited treatment options. Here, we report the protocol-specified final analysis of overall survival and endpoints by trophoblast cell-surface antigen 2 (Trop-2) expression and other variables.
In this randomised, open-label, multicentre, phase 3 trial, which took place in 91 centres across North America (the USA and Canada) and Europe (Belgium, France, Germany, Italy, the Netherlands, Spain, and the UK), patients were randomly assigned (1:1) to receive sacituzumab govitecan or chemotherapy (eribulin, vinorelbine, capecitabine, or gemcitabine). Patients had confirmed HR+ and HER2– locally recurrent inoperable or metastatic breast cancer and had received at least one previous endocrine therapy, a taxane, and a CDK4/6 inhibitor in any setting and two to four previous chemotherapy regimens for metastatic disease. The primary endpoint was progression-free survival (previously reported and not included in this analysis), and secondary endpoints included overall survival, objective response rate (ORR), and patient-reported outcomes. Overall survival was assessed using stratified log-rank tests and Cox regression. Trop-2 expression was assessed in tumour tissue by immunohistochemistry. In the statistical testing hierarchy, ORR and patient-reported outcomes were tested sequentially if overall survival was significant. This study is registered with ClinicalTrials.gov, NCT03901339.
At the data cutoff date of July 1, 2022, 543 of 776 screened patients were randomly assigned between May 30, 2019, and April 5, 2021, with 272 patients in the sacituzumab govitecan group and 271 patients in the chemotherapy group. With a 12·5-month (IQR 6·4–18·8) median follow-up, 390 deaths occurred among 543 patients. Overall survival was significantly improved with sacituzumab govitecan versus chemotherapy (median 14·4 months [95% CI 13·0–15·7] vs 11·2 months [10·1–12·7]; hazard ratio [HR] 0·79, 95% CI 0·65–0·96; p=0·020); survival benefit was consistent across Trop-2 expression-level subgroups. ORR was significantly improved with sacituzumab govitecan compared with chemotherapy (57 [21%] patients vs 38 [14%]; odds ratio 1·63 [95% CI 1·03–2·56]; p=0·035), as was time to deterioration of global health status and quality of life (median 4·3 months vs 3·0 months; HR 0·75 [0·61–0·92]; p=0·0059) and fatigue (median 2·2 months vs 1·4 months; HR 0·73 [0·60–0·89]; p=0·0021). The safety profile of sacituzumab govitecan was consistent with previous studies (including the TROPiCS-02 primary analysis and the ASCENT trial). One fatal adverse event (septic shock caused by neutropenic colitis) was determined to be related to sacituzumab govitecan treatment.
Sacituzumab govitecan demonstrated statistically significant and clinically meaningful benefit over chemotherapy, with a 3·2-month median overall survival improvement and a manageable safety profile. These data support sacituzumab govitecan as a new treatment option for patients with pretreated, endocrine-resistant HR+ and HER2– metastatic breast cancer.
Author Affiliations1Department of Medicine, University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA; 2Medical Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA; 3Department of Obstetrics and Gynaecology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; 4Oncology Department, International Breast Cancer Centre, Pangaea Oncology, Quiron Group, Barcelona, Spain; 5Medica Scientia Innovation Research, Barcelona, Spain; 6Universidad Europea de Madrid, Faculty of Biomedical and Health Sciences, Department of Medicine, Madrid, Spain; 7Barts Cancer Institute, Queen Mary University of London, London, UK; 8Institut Curie, MediS5cal Oncology Department and D3i, Paris, France; 9Department of Medical Oncology, Centre Léon Bérard, Lyon, France; 10Cancer Research Centre of Lyon, UMR Inserm 1052, CNRS 5286, Lyon, France; 11Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain; 12Institut Claudius Regaud, IUCT-Oncopole, Toulouse, France; 13Hospital Universitari Vall D’Hebron, Barcelona, Spain; 14Memorial Sloan Kettering Cancer Center, New York, NY, USA; 15Weill Cornell Medical College, New York, NY, USA; 16Gilead Sciences, Foster City, CA, USA; 17Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA