Sacituzumab Govitecan in Untreated, Advanced Triple-Negative Breast Cancer

Author(s): Javier Cortés, M.D.^1,2,3,4,5,6; Kevin Punie, M.D.⁷; Carlos Barrios, M.D.⁸; Sara A. Hurvitz, M.D.⁹; Andreas Schneeweiss, M.D.^10,11; Joohyuk Sohn, M.D.¹²; Eriko Tokunaga, M.D.¹³; Adam Brufsky, M.D.¹⁴; Yeon Hee Park, M.D.¹⁵; Binghe Xu, M.D.¹⁶; Roberto Hegg, M.D.¹⁷; Mafalda Oliveira, M.D.¹⁸; Alessandra Fabi, M.D.¹⁹; Natalya Vaksman, Pharm.D.²⁰; Theresa Valdez, Pharm.D.²⁰; Xinrui Zhang, Ph.D.²⁰; Catherine Lai, Pharm.D.²⁰; Sara M. Tolaney, M.D.²¹; the ASCENT-03 Clinical Trial Investigators*;

Source: DOI: 10.1056/NEJMoa2511734

Dr. Anjan Patel's Thoughts

ASCENT-03 shows that in first-line, PD-1/PD-L1–ineligible advanced TNBC, sacituzumab improves PFS to 9.7 vs 6.9 months and extends median duration of response (DOR) to 12.2 vs 7.2 months, with similar overall response rate (ORR) (48% vs 46%) and immature overall survival (OS) (21.5 vs 20.2 months) Grade ≥3. Adverse events (AEs) were comparable (66% vs 62%), but sacituzumab had more neutropenia and diarrhea, fewer discontinuations (4% vs 12%), and early-cycle infection-related deaths in patients without primary G-CSF. For PD-1/PD-L1–ineligible mTNBC, SG offers more durable control than chemo with manageable myelosuppression — so consider SG first-line and start G-CSF early in higher-risk patients.

BACKGROUND

Patients with previously untreated, locally advanced, unresectable or metastatic triple-negative breast cancer who are not candidates for inhibitors of programmed cell death protein 1 (PD-1) or programmed death ligand 1 (PD-L1) have limited treatment options.

METHODS

In this international, phase 3, open-label, randomized trial, we enrolled patients with previously untreated, advanced triple-negative breast cancer who were not candidates for PD-1 or PD-L1 inhibitors owing to previous use or coexisting conditions. Patients had either PD-L1–negative tumors with a combined positive score (CPS; the number of PD-L1–staining tumor cells, lymphocytes, and macrophages divided by the total number of viable tumor cells, multiplied by 100) of less than 10 or PD-L1–positive tumors with a CPS of 10 or higher and were assigned in a 1:1 ratio to receive sacituzumab govitecan or chemotherapy (paclitaxel, nanoparticle albumin-bound paclitaxel, or gemcitabine plus carboplatin). The primary end point was progression-free survival, assessed by blinded independent central review. Secondary end points included overall survival, objective response, the duration of response, and safety. Research Summary Sacituzumab Govitecan in Advanced Triple-Negative Breast Cancer

RESULTS

Among 558 patients, median progression-free survival was 9.7 months (95% confidence interval [CI], 8.1 to 11.1) with sacituzumab govitecan and 6.9 months (95% CI, 5.6 to 8.2) with chemotherapy (stratified hazard ratio for disease progression or death, 0.62; 95% CI, 0.50 to 0.77; P

CONCLUSIONS

Sacituzumab govitecan led to significantly longer progression-free survival than chemotherapy among patients with advanced triple-negative breast cancer who were not candidates for treatment with PD-1 or PD-L1 inhibitors. The incidence of adverse events of grade 3 or higher with sacituzumab govitecan was similar to that with chemotherapy, but adverse events were common. (Funded by Gilead Sciences; ASCENT-03 ClinicalTrials.gov number, NCT05382299.)

Author Affiliations

¹International Breast Cancer Center, Pangaea Oncology, Quiron Group, Barcelona; ²IOB Madrid, Institute of Oncology, Hospital Beata María Ana, Madrid; ³Oncology Department, Hospital Universitario Torrejón, Ribera Salud Group, Madrid; ⁴Universidad Europea de Madrid, Faculty of Biomedical and Health Sciences, Department of Medicine, Madrid; ⁵Medica Scientia Innovation Research, Barcelona; ⁶Medica Scientia Innovation Research, Ridgewood, NJ; ⁷Medical Oncology, Oncology Center Antwerp, Ziekenhuis aan de Stroom, Antwerp, Belgium; ⁸Latin American Cooperative Oncology Group, Porto Alegre, Brazil; ⁹Department of Medicine, University of Washington Medicine, Clinical Research Division, Fred Hutchinson Cancer Center, Seattle; ¹⁰Heidelberg University Hospital, Heidelberg, Germany; ¹¹German Cancer Research Center, Heidelberg, Germany; ¹²Yonsei Cancer Center, Seoul, South Korea; ¹³National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan; ¹⁴Hillman Cancer Center, Magee-Womens Hospital, University of Pittsburgh Medical Center, Pittsburgh; ¹⁵Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; ¹⁶Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing; ¹⁷University of São Paulo, São Paulo; ¹⁸Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology, Vall d’Hebron Barcelona Hospital Campus, Barcelona; ¹⁹Precision Medicine Unit in Senology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome; ²⁰Gilead Sciences, Foster City, CA; ²¹Dana–Farber Cancer Institute, Harvard Medical School, Boston

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