The approval expands first-line options for adults with unresectable locally advanced or metastatic TNBC: monotherapy sacituzumab govitecan-hziy for patients who are not candidates for PD-1/PD-L1 inhibitor–based therapy, and sacituzumab govitecan-hziy plus pembrolizumab for patients with PD-L1 CPS ≥ 10 tumors. Eligible trial populations included adults with unresectable locally advanced or metastatic TNBC who had not received prior systemic therapy for advanced disease; monotherapy was evaluated in patients who were not candidates for PD-1/PD-L1 inhibitor therapy and the combination was evaluated in patients with PD-L1 CPS ≥ 10 disease. What remains to be defined is how these regimens affect long-term overall survival and the optimal sequencing compared with existing first-line pembrolizumab-plus-chemotherapy approaches in broader clinical populations?

What is sacituzumab govitecan-hziy (Trodelvy) approved for?

Trodelvy is approved for the first-line treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) as a single agent for patients who are not candidates for PD-1 or PD-L1 inhibitor–based therapy. It is also approved in combination with pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph for first-line treatment of adults with unresectable locally advanced or metastatic TNBC whose tumors express PD-L1 with a Combined Positive Score (CPS ≥ 10) as determined by an FDA-authorized test.

How does sacituzumab govitecan-hziy work?

Sacituzumab govitecan-hziy is a Trop-2–directed antibody-drug conjugate composed of a humanized antibody that recognizes Trop-2 linked to the active metabolite of irinotecan, SN-38. Pharmacology data indicate the ADC binds Trop-2 on cancer cells, is internalized, and releases SN-38 via linker hydrolysis; SN-38 inhibits topoisomerase I, preventing re-ligation of single-strand DNA breaks and leading to apoptosis and tumor cell death.

What is the recommended dose of sacituzumab govitecan-hziy?

The recommended dosage of TRODELVY as a single agent or in combination with pembrolizumab is 10 mg/kg administered as an intravenous infusion on Days 1 and 8 of each 21-day cycle, continued until disease progression or unacceptable toxicity. (consult current prescribing information for full dosing guidance)

What are the most common side effects of sacituzumab govitecan-hziy?

The label identifies neutropenia, diarrhea, decreased leukocyte count, decreased neutrophil count, decreased hemoglobin, nausea, decreased lymphocyte count, fatigue, and alopecia among the most common adverse reactions. In single-agent use (incidence ≥25%), other common events included increased glucose, constipation, vomiting, decreased albumin, increased alkaline phosphatase, decreased appetite, abdominal pain, decreased creatinine clearance, decreased magnesium, and decreased potassium. The combination with pembrolizumab had overlapping and additional events reported with incidence ≥25%, including increased alanine aminotransferase and aspartate aminotransferase, rash, and others. The label contains boxed warnings for severe neutropenia and severe diarrhea and provides management recommendations including G-CSF prophylaxis where indicated and guidance on withholding or reducing doses for adverse reactions.