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Clinical Trial
. 2023 Oct 21;402(10411):1423-1433.
doi: 10.1016/S0140-6736(23)01245-X. Epub 2023 Aug 23.

Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trial

Hope S Rugo  1 , Aditya Bardia  2 , Frederik Marmé  3 , Javier Cortés  4 , Peter Schmid  5 , Delphine Loirat  6 , Olivier Trédan  7 , Eva Ciruelos  8 , Florence Dalenc  9 , Patricia Gómez Pardo  10 , Komal L Jhaveri  11 , Rosemary Delaney  12 , Theresa Valdez  12 , Hao Wang  12 , Monica Motwani  12 , Oh Kyu Yoon  12 , Wendy Verret  12 , Sara M Tolaney  13
Affiliations
Free article
Clinical Trial

Overall survival with sacituzumab govitecan in hormone receptor-positive and human epidermal growth factor receptor 2-negative metastatic breast cancer (TROPiCS-02): a randomised, open-label, multicentre, phase 3 trial

Hope S Rugo et al. Lancet. .
Free article

Abstract

Background: 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.

Methods: 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.

Findings: 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.

Interpretation: 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.

Funding: Gilead Sciences.

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Conflict of interest statement

Declaration of interests HSR reports honoraria from Puma Biotechnology, Mylan, and Samsung Bioepis, and institutional research funding from Macrogenics, OBI Pharma, Pfizer, Novartis, Lilly, Genentech, Merck, Odonate Therapeutics, Daiichi Sankyo, Seattle Genetics, Sermonix Pharmaceuticals, AstraZeneca, Gilead Sciences, and Ayala Pharmaceuticals. AB reports institutional research funding from Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health and Menarini, Immunomedics and Gilead Sciences, Daiichi Sankyo, and AstraZeneca, and Eli Lilly, and consulting fees from Pfizer, Novartis, Genentech, Merck, Radius Health and Menarini, Immunomedics and Gilead Sciences, Sanofi, Daiichi Sankyo, AstraZeneca, Phillips, Eli Lilly, and Foundation Medicine. FM reports institutional research funding from Roche, Novartis, AstraZeneca, GSK and Tesaro, MED, Clovis, Vaccibody, Gilead Sciences, and Eisai; consulting fees from AstraZeneca, GSK and Tesaro, Pfizer, Eisai, Gilead Sciences, Vaccibody, and GenomicHealth; honoraria from AstraZeneca, Clovis, GSK and Tesaro, Eli Lilly, Novartis, Pfizer, Roche, Myriad Genetics, PharmaMar, Eisai, MSD, Immunomedics and Gilead Sciences, Pierre-Fabre, Agendia, Genomic Health, and Seattle Genetics; support for meeting attendance and travel from Pfizer, Roche, and AstraZeneca; and participation on a data safety monitoring board or advisory board for Palleos and Amgen. JC reports institutional research funding from Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta, Servier Affaires, Bayer Healthcare, Eisai, F Hoffman-La Roche, Guardant Health, Merck Sharp & Dohme, Pfizer, Piqur Therapeutics, Puma Biotechnology, and Queen Mary University of London; consulting fees from 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 Sciences, Menarini, Zymeworks, Reveal Genomics, and Expres2ion Biotechnologies; honoraria from Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck, Sharp & Dohme, and Daiichi Sankyo; travel and accommodations from Roche, Novartis, Eisai, Pfizer, Daiichi Sankyo, AstraZeneca, and Gilead Sciences; stock ownership from MedSIR and Nektar Pharmaceuticals; and several patents. PS reports institutional research funding from Astellas, AstraZeneca, Genentech, Novartis, Oncogenex, Roche, and Medivation; consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim, Merck, Novartis, Pfizer, Puma, Roche, Eisai, and Celgene; and spouse's employment at Roche. DL reports honoraria from AstraZeneca, Novartis, MSD, Lilly, Amgen, Eisai, and Gilead Sciences; consulting fees from Roche, AstraZeneca, Pfizer, Novartis, MSD, Immunomedics, Pharma4D, Daiichi Sankyo, Lilly, Amgen, and Eisai; and travel and accommodations from Roche, AstraZeneca, Pfizer, Novartis, MSD, Gilead Sciences, and Amgen. OT reports institutional research funding from Bristol Myers Squibb and MSD; honoraria from Roche, Pfizer, Novartis-Sandoz, Lilly, MSD, AstraZeneca, Pierre Fabre, Seagen, Daiichi Sankyo, Gilead Sciences, Eisai, and Stemline; travel and accommodations from Roche, Pfizer, Novartis-Sandoz, Lilly, MSD, AstraZeneca, Seagen, Daiichi Sankyo, and Gilead Sciences; and participation on a data safety monitoring board or advisory board for Roche, Pfizer, Novartis-Sandoz, Lilly, MSD, AstraZeneca, Seagen, and Daiichi Sankyo. EC reports consulting fees from Novartis, Lilly, Pfizer, Roche, AstraZeneca, and Daiichi Sankyo; speaker's bureau from Lilly, Pfizer, AstraZeneca, and Daiichi Sankyo; and travel and accommodations from Pfizer and Roche. KLJ reports consulting fees from Novartis, Pfizer, Bristol Myers Squibb, Jounce Therapeutics, Taiho Oncology, Genentech, Synthon, AbbVie, Eisai, AstraZeneca, Blueprint Medicine, Daiichi Sankyo, Sun Pharma Advanced Research Company, Gilead Sciences, Seattle Genetics, and Lilly Pharmaceuticals and Loxo Oncology; and institutional research funding from Novartis, Clovis Oncology, Genentech, AstraZeneca, ADC Therapeutics, Novita Pharmaceuticals, Debio Pharmaceuticals, Pfizer, Lilly Pharmaceuticals and Loxo Oncology, Zymeworks, Immunomedics and Gilead Sciences, Puma Biotechnology, and Merck Pharmaceuticals. RD, TV, HW, MM, and OKY report employment by and stock ownership in Gilead Sciences. WV reports previous employment by and stock ownership in Genentech and employment by Gilead Sciences. SMT reports institutional research funding from Gilead Sciences, AstraZeneca, Eli Lilly, Merck, Nektar, Novartis, Pfizer, Genentech and Roche, Exelixis, Bristol Myers Squibb, Eisai, Nanostring, Cyclacel, Sanofi, Odonate, and Seagen; consulting fees from AstraZeneca, Eli Lilly, Merck, Nektar, Novartis, Pfizer, Genentech and Roche, Gilead Sciences, Bristol Myers Squibb, Eisai, Nanostring, Sanofi, Odonate, Seagen, Daiichi Sankyo, Athenex, CytomX, Blueprint Medicines, Zentalis, Zymeworks, Ellipses Pharma, 4D Pharma, OncoSec, Infinity Therapeutics, BeyondSpring Pharma, OncXerna, Reveal Genomics, ARC Therapeutics, Kyowa Kirin Pharma, G1 Therapeutics, Silverback Therapeutics, Certara, Mersana Therapeutics, and OncoPep; and honoraria from Chugai, Genentech and Roche, Eisai, Gilead Sciences, AstraZeneca, and Bristol Myers Squibb. All other authors declare no competing interests.

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