By VETTAPHARMA reporter – Derek Roche: Gilead Sciences’ Trodelvy (sacituzumab govitecan-hziy) has secured major regulatory milestones in both the United States and Europe, with approvals from the U.S. Food and Drug Administration (FDA) and the European Commission (EC) for the first-line treatment of unresectable locally advanced or metastatic triple-negative breast cancer.
Together, the approvals establish Trodelvy as a new first-line treatment option and significantly expand access to the antibody-drug conjugate (ADC) for patients with one of the most aggressive forms of breast cancer.
In the United States, the FDA approved Trodelvy as monotherapy for patients who are not candidates for PD-(L)1 inhibitor-based therapy, and in combination with Keytruda® (pembrolizumab) or Keytruda Qlex™ for patients whose tumors express PD-L1 (CPS ≥10). In Europe, the European Commission approved Trodelvy as the first antibody-drug conjugate for first-line metastatic triple-negative breast cancer in patients who are not candidates for PD-(L)1 inhibitors, representing the first new treatment option in more than 20 years for this patient population.
The approvals are supported by the pivotal Phase 3 ASCENT-03 and ASCENT-04/KEYNOTE-D19 studies. In ASCENT-03, Trodelvy monotherapy reduced the risk of disease progression or death by 38% compared with chemotherapy in patients who were ineligible for PD-(L)1 inhibitors. In ASCENT-04, Trodelvy combined with pembrolizumab reduced the risk of disease progression or death by 35% compared with pembrolizumab plus chemotherapy in patients with PD-L1-positive disease.
Trodelvy also demonstrated substantially more durable responses than chemotherapy. Median duration of response reached 12.2 months versus 7.2 months in ASCENT-03 and 16.5 months versus 9.2 months in ASCENT-04. The European Commission noted that the approval confirms the clinical benefit of introducing Trodelvy earlier in the treatment pathway for patients with metastatic triple-negative breast cancer.
According to Gilead, more than 75,000 patients have been treated with Trodelvy globally since 2020. The therapy is currently approved in more than 60 countries for second-line or later metastatic triple-negative breast cancer and in over 50 countries for certain patients with pre-treated hormone receptor-positive/HER2-negative metastatic breast cancer. Trodelvy is also the only Trop-2-directed antibody-drug conjugate to demonstrate an overall survival benefit in two distinct metastatic breast cancer settings and the only ADC with four positive Phase 3 trials in HER2-negative metastatic breast cancer.
Trodelvy carries a Boxed Warning in the United States for severe or fatal neutropenia and diarrhea. The most common adverse reactions include neutropenia, diarrhea, nausea, fatigue, alopecia, constipation, and vomiting.
Quick FAQs
1. What Is Trodelvy?
Trodelvy (sacituzumab govitecan-hziy) is a Trop-2-directed antibody-drug conjugate (ADC) developed by Gilead Sciences for the treatment of metastatic breast cancer.
2. What Happened?
The FDA and the European Commission approved Gilead’s Trodelvy for first-line treatment of metastatic triple-negative breast cancer, expanding its use to earlier stages of treatment.
3. What Studies Supported The Approvals?
The approvals were supported by the Phase 3 ASCENT-03 and ASCENT-04/KEYNOTE-D19 trials evaluating Trodelvy as monotherapy and in combination with pembrolizumab in first-line metastatic triple-negative breast cancer.
4. What Is Metastatic Triple-Negative Breast Cancer?
Metastatic triple-negative breast cancer is an aggressive subtype of breast cancer lacking estrogen receptors, progesterone receptors, and significant HER2 expression. It accounts for approximately 15% of all breast cancers and is associated with limited treatment options and poor long-term survival.
5. What Were The Key Results?
Trodelvy reduced the risk of disease progression or death by 38% as monotherapy in ASCENT-03 and 35% in combination with pembrolizumab in ASCENT-04, while substantially extending the duration of response compared with chemotherapy.
6. Why Is This Important?
The parallel FDA and European Commission approvals establish Trodelvy as a new first-line treatment option for metastatic triple-negative breast cancer and expand access to an antibody-drug conjugate earlier in the disease course across major global markets.
