FDA Approves Sacituzumab Govitecan for First-Line Treatment of Advanced Triple-Negative Breast Cancer

The FDA has approved sacituzumab govitecan-hziy (Trodelvy; Gilead Sciences) both as monotherapy and in combination with pembrolizumab (Keytruda; Merck) for the first-line treatment of adults with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC), marking a significant expansion of treatment options for this aggressive breast cancer subtype. The approvals, announced on June 24, 2026, are supported by findings from the phase 3 ASCENT-03 (NCT05382299) and ASCENT-04/KEYNOTE-D19 (NCT05382286) clinical trials.¹

Expanding First-Line Options in Triple-Negative Breast Cancer

TNBC accounts for approximately 10% to 15% of all breast cancers and is associated with an aggressive clinical course, early recurrence, and poorer outcomes compared with other breast cancer subtypes.² Historically, treatment options for patients with advanced TNBC have been limited, particularly for those who are not candidates for immunotherapy.

Sacituzumab govitecan is a TROP-2-directed antibody-drug conjugate that delivers the topoisomerase I inhibitor SN-38 directly to tumor cells.³ The agent was previously approved for patients with metastatic TNBC who had received prior therapies, but the new indications move its use into the first-line setting.¹

The first approval is for sacituzumab govitecan monotherapy in adults with unresectable locally advanced or metastatic TNBC who are not candidates for PD-1 or PD-L1 inhibitor-based treatment. The second authorizes the agent’s use in combination with pembrolizumab for those whose tumors express PD-L1 with a combined positive score (CPS) of 10 or greater, as determined by an FDA-authorized test.¹

ASCENT-03 Demonstrates Improved Progression-Free Survival

The monotherapy approval was based on data from the phase 3 ASCENT-03 trial, which enrolled 558 patients with previously untreated, unresectable locally advanced or metastatic TNBC who were not candidates for PD-1 or PD-L1 inhibitor therapy.^1,4 Patients received either sacituzumab govitecan or physician’s choice chemotherapy.

Investigators reported a median progression-free survival (PFS) of 9.7 months with sacituzumab govitecan compared with 6.9 months for chemotherapy, representing an approximate 38% reduction in the risk of disease progression or death (HR, 0.62 [95% CI, 0.50-0.77]; P < .001).^1,4 Confirmed objective response rates (ORRs) were approximately 50% and 47%, respectively, whereas overall survival (OS) data remain immature.¹

Published findings from ASCENT-03 also demonstrated a longer median duration of response with sacituzumab govitecan (12.2 months) compared with chemotherapy (7.2 months).⁴

Combination Therapy Shows Benefit in PD-L1–Positive Disease

The second approval was supported by results from the ASCENT-04/KEYNOTE-D19 study, which enrolled 443 patients with previously untreated locally advanced or metastatic TNBC and PD-L1-positive tumors (CPS ≥10).¹

Patients treated with sacituzumab govitecan plus pembrolizumab achieved a median PFS of 11.2 months compared with 7.8 months for chemotherapy plus pembrolizumab (HR, 0.65 [95% CI, 0.51-0.84]; P = .0009).¹ Confirmed ORRs were 61% and 55%, respectively. As with ASCENT-03, OS data are not yet mature.¹

Pharmacist Considerations for Clinical Practice

The expanded role of sacituzumab govitecan in first-line TNBC highlights several important considerations for oncology pharmacists. The prescribing information includes a boxed warning for severe or life-threatening neutropenia and diarrhea, requiring proactive monitoring and supportive care strategies.¹ Pharmacists play a key role in patient counseling, toxicity management, and ensuring appropriate dose modifications when adverse events occur.

Additionally, pharmacists may help identify patients eligible for treatment by reviewing PD-L1 testing results and collaborating with multidisciplinary care teams on treatment selection. Given the growing use of biomarker-driven therapies in breast cancer treatment, pharmacists remain integral in optimizing therapy, monitoring safety, and supporting adherence throughout treatment.

The FDA noted that these approvals were reviewed under Project Orbis, an international collaboration designed to accelerate access to promising oncology therapies across participating regulatory agencies.¹

REFERENCES

1. FDA approves sacituzumab govitecan-hziy as monotherapy and in combination with pembrolizumab for first-line treatment of triple-negative breast cancer. FDA. June 24, 2026. Accessed June 24, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-sacituzumab-govitecan-hziy-monotherapy-and-combination-pembrolizumab-first-line

2. Triple-negative Breast Cancer. American Cancer Society. Updated June 25, 2025. Accessed June 24, 2026. https://www.cancer.org/cancer/types/breast-cancer/about/types-of-breast-cancer/triple-negative.html

3. Highlights of Prescribing Information: Trodelvy. Updated March 2025. Accessed June 24, 2026. https://www.gilead.com//media/files/pdfs/medicines/oncology/trodelvy/trodelvy_pi.pdf

4. Cortés J, Punie K, Barrios C, et al. Sacituzumab Govitecan in Untreated, Advanced Triple-Negative Breast Cancer. New England Journal of Medicine. 2025;393(19):1912-1925. doi:10.1056/nejmoa2511734