The FDA has approved sacituzumab govitecan-hziy for patients with unresectable locally advanced or metastatic hormone receptor-positive, HER2-negative breast cancer.
The FDA has approved sacituzumab govitecan-hziy (Trodelvy) for the treatment of adult patients with unresectable locally advanced or metastatic hormone receptor (HR)–positive, HER2-negative breast cancer following prior treatment with endocrine-based therapy and at least 2 additional systemic therapies in the metastatic setting. The agent comes with a boxed warning for neutropenia and diarrhea.1
The approval is supported by findings from the TROPiCS-02 study (NCT03901339), in which sacituzumab govitecan outperformed treatment of physician’s choice (TPC; single-agent chemotherapy) and drew a statistically significant and clinically meaningful overall survival (OS) benefit in this setting. The median OS with the antibody-drug conjugate was 14.4 months vs 11.2 months with TPC (HR, 0.79; 95% CI, 0.65-0.96; P = .02).
Moreover, the median progression-free survival (PFS) with sacituzumab govitecan was 5.5 months vs 4.0 months with TPC, leading to a 34% reduction in the risk of disease progression or death with sacituzumab govitecan (HR, 0.66; 95% CI, 0.53-0.83; P = .0003). After 1 year, 21% of patients who had received sacituzumab govitecan were progression-free compared with 7% on TPC.
The recommended dose for sacituzumab govitecan is 10 mg/kg once weekly on days 1 and 8 of continuous 21-day treatment cycles. Premedication for infusion reactions and chemotherapy-induced nausea and vomiting is recommended.2
Patients should be monitored during the infusion and for 30 minutes thereafter. The first infusion should be given over 3 hours; if the infusion is well tolerated, future doses may be given over 1 to 2 hours.2
Sacituzumab govitecan is now recommended as a category 1, preferred treatment for patients with metastatic HR-positive/HER2-negative breast cancer by the National Comprehensive Cancer Network® Clinical Practice Guidelines in Oncology.
“Despite decades of advances, people living with pre-treated HR-positive/HER2-negative metastatic breast cancer need new treatment options. Nearly all people with this type of breast cancer will eventually develop resistance to endocrine-based therapies and progress on available chemotherapies,” principal investigator Hope S. Rugo, MD, professor of medicine and director, Breast Oncology and Clinical Trials Education at the University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, said in a press release.1
“This approval is significant for the breast cancer community,” she added. “We have had limited options to offer patients after endocrine-based therapy and chemotherapy, and to see a clinically meaningful survival benefit of more than 3 months with a quality-of-life benefit for these women is exceptional.”
The TROPiCs-02 study randomly assigned 543 patients 1:1 to receive either sacituzumab govitecan or single-agent chemotherapy (eribulin, capecitabine, gemcitabine, or vinorelbine). Participants had HR-positive/HER2-negative metastatic breast cancer and had already received endocrine therapy, CDK4/6 inhibitor and 2 to 4 lines of chemotherapy for metastatic disease. HER2 negativity was defined as an immunohistochemistry (IHC) score of 0, IHC 1+, or IHC 2+, with a negative in-situ hybridization test.
No new safety signals were identified in TROPiCs-02; the safety profile was consistent with what had been previously reported. The most common serious adverse events (AEs) were diarrhea (5%), febrile neutropenia (4%), neutropenia (3%), and abdominal pain, colitis, neutropenic colitis, pneumonia, and vomiting (2% each). The most common grade 3/4 abnormalities were reduced neutrophils and leukocytes. No cases of interstitial lung disease were reported in the trial.
The prescribing label comes with a boxed warning for neutropenia.2 Because of this, blood counts should be monitored throughout treatment. If a patients’ absolute neutrophil count drops below 1500/mm3 or they develop a neutropenic fever, treatments should be withheld. Granulocyte colony-stimulating factor may be considered as a secondary prophylaxis. For patients who develop febrile neutropenia, anti-infective treatment should be initiated without delay.
The agent also has a boxed warning for severe diarrhea. Patients should be monitored for diarrhea and receive fluids and electrocytes as needed. For patients who develop early diarrhea of any severity, atropine should be administered, if it is not contraindicated. In the event of late onset diarrhea, loperamide should be given. If severe diarrhea occurs, treatment should be withheld until the AE resolves to a grade 1 or less, at which point treatment can continue.
The prescribing label also comes with warnings for hypersensitivity and infusion-related reactions, nausea and vomiting, and embryo-fetal toxicity. Of note, patients with reduced UGT1A1 activity are at an increased risk of AEs. For this reason, the concomitant administration with UTGIA1 inhibitors should be avoided. Concomitant treatment with UGT1A1 should also be avoided.
“The FDA approval is an important step forward for both women and men living with metastatic breast cancer, especially for those individuals whose tumor is no longer responding to endocrine-based therapies and who are facing a poor prognosis,” Laura Carfang, executive director of SurvivingBreastCancer.org, stated in the press release.1 “We need to combat this terrible disease, and all options that potentially slow its progress and extend life for those living with metastatic breast cancer are welcomed.”