Feb 2023: For patients with unresectable locally advanced or metastatic hormone receptor (HR)-positive, HER2-negative (IHC 0, IHC 1+, or IHC 2+/ISH-) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting, the Food and Drug Administration (FDA) has approved sacituzumab govitecan-hziy (Trodelvy, Gilead Sciences, Inc.).
TROPiCS-02 (NCT03901339), a multicenter, open label, randomised study involving 543 patients with unresectable locally advanced or metastatic HR-positive, HER2-negative breast cancer whose disease progressed after receiving a CDK 4/6 inhibitor, endocrine therapy, and a taxane in any setting, evaluated the effectiveness in these patients. At least two previous chemotherapies were administered to patients with metastatic disease (one of which could be in the neoadjuvant or adjuvant setting if recurrence occurred within 12 months).
Patients were randomly assigned (1:1) to receive either single agent chemotherapy (n = 271) or sacituzumab govitecan-hziy, 10 mg/kg as an intravenous infusion, on Days 1 and 8 in a 21-day cycle. Prior to randomization, the investigator selected a single agent chemotherapy regimen from one of the following options: capecitabine (n=22), vinorelbine (n=63), gemcitabine (n=56), or eribulin (n=130). Prior chemotherapy regimens for metastatic disease (2 vs. 3-4), visceral metastasis (Yes or No), and endocrine therapy in the metastatic setting for at least 6 months were all used to stratify randomization (Yes or No). Patients received treatment up until the onset of unacceptable side effects.
Progression-free survival (PFS), as defined by blinded independent central review in accordance with RECIST v1.1, served as the primary efficacy outcome measure. Overall survival was a crucial secondary efficacy outcome metric (OS). The median PFS for the sacituzumab govitecan-hziy arm was 5.5 months (95% CI: 4.2, 7.0) and for the single agent chemotherapy arm was 4 months (95% CI: 3.1, 4.4) (hazard ratio [HR] of 0.661 [95% CI: 0.529, 0.826]; p-value=0.0003). For those getting sacituzumab govitecan-hziy, the median OS was 14.4 months (95% CI: 13.0, 15.7), whereas for those receiving single agent chemotherapy, it was 11.2 months (95% CI: 10.1, 12.7) (HR of 0.789 [95% CI: 0.646, 0.964]; p-value=0.0200).
Reduced leukocyte count (88%), reduced neutrophil count (83%), decreased haemoglobin (73%), decreased lymphocyte count (65%), diarrhoea (62%), fatigue (60%), nausea (59%), alopecia (48%), increased glucose (37%), constipation (34%), and decreased albumin (32%) were the most frequent adverse events (25%) in patients treated with sacituzumab govitecan-hziy in TROPiCS-02.
A weekly intravenous infusion of 10 mg/kg of sacituzumab govitecan-hziy should be delivered on Days 1 and 8 of a 21-day therapy cycle until disease progression or intolerable toxicity, whichever comes first.
Project Orbis, an initiative of the FDA Oncology Center of Excellence, was used to carry out this review. International partners can simultaneously submit and review oncology medications using the infrastructure provided by Project Orbis. FDA worked together on this review with the Therapeutic Goods Administration (TGA) of Australia, Health Canada, and Swissmedic. At the other regulatory organizations, the application reviews are still proceeding.