FDA Approves Sacituzumab Govitecan-hziy for HR-positive Advanced Breast Cancer

On 3 February 2023, the US Food and Drug Administration (FDA) approved sacituzumab govitecan-hziy (Trodelvy, Gilead Sciences, Inc.) for patients with unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (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.

Full prescribing information for Trodelvy is available here.

Efficacy was evaluated in TROPiCS-02 (NCT03901339), a multicentre, open label, randomised study in 543 patients with unresectable locally advanced or metastatic HR-positive, HER2-negative breast cancer whose disease progressed after the following in any setting: a CDK 4/6 inhibitor, endocrine therapy, and a taxane. Patients received at least two prior chemotherapies in the metastatic setting (one of which could be in the neoadjuvant or adjuvant setting if recurrence occurred within 12 months).

Patients were randomised (1:1) to sacituzumab govitecan-hziy, 10 mg/kg as an intravenous infusion, on Days 1 and 8 of a 21-day cycle (n=272) or single agent chemotherapy (n=271). Single agent chemotherapy was determined by the investigator before randomisation from one of the following choices: eribulin (n=130), vinorelbine (n=63), gemcitabine (n=56), or capecitabine (n=22). Randomisation was stratified by the following factors: 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 (yes or no). Patients were treated until disease progression or unacceptable toxicity.

The primary efficacy outcome measure was progression-free survival (PFS) determined by blinded independent central review per RECIST v1.1. A key secondary efficacy outcome measure was overall survival (OS). Median PFS was 5.5 months (95% confidence interval [CI] 4.2, 7.0) in the sacituzumab govitecan-hziy arm and 4 months (95% CI 3.1, 4.4) in the single agent chemotherapy arm (hazard ratio [HR] of 0.661, 95% CI 0.529, 0.826; p-value = 0.0003). Median OS was 14.4 months for those receiving sacituzumab govitecan-hziy (95% CI 13.0, 15.7) and 11.2 months (95% CI 10.1, 12.7) for those receiving single agent chemotherapy (HR of 0.789, 95% CI 0.646, 0.964; p-value = 0.0200).

The most common adverse events (≥25%) in patients treated with sacituzumab govitecan-hziy in TROPiCS-02 including laboratory abnormalities, were decreased leukocyte count (88%), decreased 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%).

The recommended sacituzumab govitecan-hziy dose is 10 mg/kg administered as an intravenous infusion once weekly on Days 1 and 8 of 21-day treatment cycles until disease progression of unacceptable toxicity.

This review was conducted under Project Orbis, an initiative of the FDA’s Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with the Australian Therapeutic Goods Administration, Health Canada, and Switzerland’s Swissmedic. The application reviews are ongoing at the other regulatory agencies.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

This application was granted priority review.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA’s Oncology Center of Excellence Project Facilitate.