Sacituzumab Govitecan Receives FDA Approval for Hormone-Positive Breast Cancer

On February 3, 2022, the FDA approved sacituzumab govitecan-hziy (Trodelvy, Gilead Sciences, Inc.) for unresectable locally advanced or stage 4 metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2-negative breast cancer (HER2 IHC 0, IHC 1+ or IHC 2+/ISH-) after hormonal therapy and at least 2 systemic treatment lines for metastatic disease.

Trodelvy contains sacituzumab govitecan and is an antibody-drug conjugate , a next-generation, advanced biotechnology cancer medicine. It first received FDA approval in April 2020 for advanced triple-negative breast cancer, followed in April 2021 by approval for advanced urothelial cancer of the bladder and urinary tract. Today's approval is the drug's 3rd FDA approval.

FDA Approval Based on TROPiCS-02

We previously discussed TROPiCS-02 as "the most notable presentation at ESMO 2022" and suggested it could lead to treatment approval.

Effective endocrine treatments, including combinations with CDK4/6 inhibitors, have substantially improved overall survival in HR-positive/HER2-negative disease. When they fail, however, chemotherapy is used, and effectiveness decreases in later treatment lines.

Efficacy was evaluated in TROPiCS-02, a multicenter, open-label randomized trial involving 543 patients with unresectable locally advanced or metastatic HR-positive, HER2-negative breast cancer. Disease had progressed after a CDK4/6 inhibitor, endocrine therapy and a taxane. Patients had received at least two chemotherapy regimens for metastatic disease; one could have been neoadjuvant or adjuvant if recurrence occurred within 12 months.

Patients were randomized 1:1 to sacituzumab govitecan-hziy 10 mg/kg by intravenous infusion on days 1 and 8 of a 21-day cycle (272 patients), or single-agent chemotherapy (271). Before randomization, investigators selected eribulin (130), vinorelbine (63), gemcitabine (56) or capecitabine (22). Stratification factors were previous metastatic chemotherapy regimens (2 versus 3-4), visceral metastases (yes/no), and at least 6 months of endocrine therapy in the metastatic setting (yes/no). Treatment continued until progression or unacceptable adverse effects.

The primary efficacy endpoint was progression-free survival (PFS). Overall survival was an important secondary endpoint.

Results

• In heavily pretreated hormone receptor-positive/HER2-negative metastatic breast cancer, sacituzumab significantly improved overall survival versus physician's choice (median 14.4 versus 11.2 months; hazard ratio [HR] 0.79 [95% confidence interval (CI) 0.65-0.96; p=0.02).
• Response rates and quality of life also improved significantly, and adverse effects were manageable.
• An earlier TROPICS-02 analysis showed significant progression-free survival (PFS) benefit: median 5.5 versus 4 months.
• PFS rates at 12 months were 21% versus 7%.

In patients treated with sacituzumab govitecan in TROPiCS-02, the most common (≥25%) adverse effects, including laboratory abnormalities, were decreased leukocytes (88%), neutrophils (83%), hemoglobin (73%) and lymphocytes (65%); diarrhea (62%), fatigue (60%), nausea (59%), alopecia (48%), increased glucose (37%), constipation (34%) and decreased albumin (32%).

The recommended sacituzumab govitecan dose is 10 mg/kg by intravenous infusion once weekly on days 1 and 8 of 21-day cycles, until unacceptable adverse effects or cancer progression.

In conclusion , although TROPiCS-02's benefit was smaller than that seen with sacituzumab in triple-negative breast cancer, TROPiCS-02 demonstrated a clinically meaningful effect. Sacituzumab should now be considered among later-line options for hormone-positive/HER2-negative advanced breast cancer.