ASCO has released a rapid recommendation update to the guideline on chemotherapy and targeted therapy for endocrine-pretreated or hormone receptor–negative metastatic breast cancer, addressing the use of sacituzumab govitecan-hziy in patients with endocrine-resistant, hormone receptor–positive, HER2-negative metastatic breast cancer.1 The update was developed following the reported results from the TROPiCS-02 trial, which found a significant overall survival benefit with sacituzumab govitecan over single-agent chemotherapy in patients with endocrine-resistant, hormone receptor–positive, HER2-negative advanced breast cancer who had received two to four prior chemotherapy regimens.2
“Sacituzumab govitecan has a clearly established role in the treatment of metastatic triple-negative breast cancer. It is important for clinicians to know sacituzumab govitecan is also a treatment option for [patients with] metastatic hormone receptor–positive, HER2-negative breast cancer whose disease is endocrine-refractory,” said Expert Panel Co-Chair Beverly Moy, MD, MPH, of Massachusetts General Hospital.
Beverly Moy, MD, MPH
Under the updated guidance, patients with hormone receptor–positive, HER2-negative metastatic breast cancer who are refractory to endocrine therapy and have received at least two prior lines of chemotherapy for metastatic disease may be offered sacituzumab govitecan.
The international, randomized, phase III TROPiCS-02 trial compared the antibody-drug conjugate sacituzumab govitecan against the treatment of physician’s choice consisting of single-agent chemotherapy (eribulin, vinorelbine, capecitabine, or gemcitabine) in 543 patients with endocrine-resistant, hormone receptor–positive, HER2-negative locally recurrent inoperable or metastatic breast cancer who had received two to four prior chemotherapy regimens for metastatic disease.
As presented during the 2022 ASCO Annual Meeting and published in the Journal of Clinical Oncology, the trial met its primary endpoint, with sacituzumab govitecan demonstrating a 34% reduction in the risk of disease progression or death over chemotherapy of physician’s choice after a median follow-up of 10.2 months (hazard ratio [HR] = 0.66, 95% confidence interval [CI] = 0.53–0.83; P = .0003).3 The median progression-free survival was 5.5 vs 4.0 months, respectively. Key grade 3 or higher treatment-related events associated with sacituzumab govitecan included diarrhea (5%), febrile neutropenia (4%), and neutropenic colitis (2%). At the time of this planned interim analysis, median overall survival was not yet reached (HR = 0.84; P = .14).
At the second planned interim analysis, presented at the European Society for Medical Oncology Congress 2022, after a median follow-up of 12.5 months, the median overall survival was 14.4 months with sacituzumab govitecan vs 11.2 months with treatment of physician’s choice, indicating an overall survival benefit of more than 3 months with sacituzumab govitecan (HR = 0.79, 95% CI = 0.65–0.96; P = .020).2
“The strength of these data compelled the ASCO guideline committee to update the guideline,” Dr. Moy said.
Lisa A. Carey, MD, ScM, FASCO
This update follows an earlier August 2022 update that addressed the use of another antibody-drug conjugate, fam-trastuzumab deruxtecan-nxki, in patients with HER2-low disease, based on its demonstrated overall survival benefit over physicians’ choice of chemotherapy in the DESTINY-Breast-04 trial.4,5 In an interview with ASCO Daily News, Dr. Moy and guideline Co-Chair Lisa A. Carey, MD, ScM, FASCO, of the University of North Carolina Lineberger Comprehensive Cancer Center, noted that questions remain about how best to use these newer agents in practice.
“In light of the results of the DESTINY-Breast-04 study…, how should clinicians sequence using these antibody-drug conjugates?” Dr. Moy asked. She questioned whether there may be common mechanisms of resistance between the two antibody-drug conjugates. “We look to future research and clinical trials to help optimize the use of this important class of therapeutics,” she added.
1. Moy B, Rumble RB, Carey LA, et al: Chemotherapy and targeted therapy for endocrine-pretreated or hormone receptor-negative metastatic breast cancer: ASCO Guideline Rapid Recommendation Update. J Clin Oncol 41:1318-1320, 2023.
2. Rugo HS, Bardia A, Marmé F, et al: LBA76: Overall survival results from the phase III TROPiCS-02 study of sacituzumab govitecan vs treatment of physician’s choice in patients with HR+/HER2– metastatic breast cancer. Ann Oncol 33(suppl 7):S1386, 2022.
3. Rugo HS, Bardia A, Marmé F, et al: Sacituzumab govitecan in hormone receptor–positive/human epidermal growth factor receptor 2–negative metastatic breast cancer. J Clin Oncol 40:3365-3376, 2022.
4. Moy B, Rumble RB, Come SE, et al: Chemotherapy and targeted therapy for patients with human epidermal growth factor receptor 2-negative metastatic breast cancer that is either endocrine-pretreated or hormone receptor-negative: ASCO Guideline Update. J Clin Oncol 39:3938-3958, 2021.
5. Modi S, Jacot W, Yamashita T, et al; DESTINY-Breast04 Trial Investigators: Trastuzumab deruxtecan in previously treated HER2-low advanced breast cancer. N Engl J Med 387:9-20, 2022.
Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, February 24, 2023. All rights reserved.