Trodelvy Enters the First-Line Setting: NCCN Elevates Sacituzumab Govitecan in Metastatic TNBC

Trodelvy (sacituzumab govitecan-hziy) is a Trop-2–targeted antibody–drug conjugate developed by Gilead Sciences that delivers the topoisomerase I inhibitor payload, SN-38, to tumor cells, thereby disrupting DNA replication and promoting targeted tumor cell death. As of January 28th, 2026, the National Comprehensive Cancer Network (NCCN) guidelines list Trodelvy as a Category 1 preferred first-line treatment for patients with PD-L1–negative metastatic triple-negative breast cancer (TNBC) without germline BRCA1/2 mutations. The therapy may also be used in combination with pembrolizumab in PD-L1–positive disease; key safety considerations include boxed warnings for severe neutropenia and diarrhea, which require monitoring and supportive management during treatment. This update is supported by phase 3 clinical trial results.

Trodelvy (sacituzumab govitecan-hziy) Profile & Mechanism

• Manufacturer: Gilead Sciences
• Therapy Type: Antibody-drug conjugate (ADC)
  • Target: Trop-2
  • Payload: SN-38 (topoisomerase I inhibitor)
• Mechanism of Action: First-in-class ADC containing a proprietary hydrolyzable linker (CL2A) attached to SN-38.
  • After binding, the SN-38 payload is released, enabling topoisomerase I inhibition that disrupts DNA replication and leads to targeted tumor cell death.

NCCN Recommendation

• NCCN Update: Trodelvy is now a category 1 preferred first-line treatment option for PD-L1 negative metastatic TNBC with no germline BRCA1/2 pathogenic variant.
  • This update is based on positive results from two Phase 3 studies (ASCENT-03 & ASCENT-04) evaluating sacituzumab govitecan in the first-line metastatic TNBC setting.
• Combination Therapy:
  • First-line metastatic TNBC with PD-L1-positive tumors.
  • Used in combination with pembrolizumab as a category 2A preferred option.
• Current Approved Indications:
  • Adults with unresectable locally advanced or metastatic TNBC who have received≥ 2 prior systemic therapies (including ≥ 1 for metastatic disease).
  • Adults with HR-positive/HER2-negative metastatic breast cancer who received endocrine therapy and ≥ 2 additional systemic therapies in the metastatic setting.

Safety Profile

• Boxed Warning: Severe or life-threatening neutropenia and severe diarrhea.
  • Neutropenia: May occur and requires monitoring of blood counts during treatment.
    • Therapy may be withheld if neutrophil counts fall below recommended thresholds or if febrile neutropenia develops.
  • Diarrhea: Severe diarrhea can occur and requires monitoring and supportive care.
    • Treatment interruption or dose modification may be required.
• Hypersensitivity Risk: Trodelvy is contraindicated in patients with severe hypersensitivity reactions to the drug.
• Supportive Care: Safety management may include growth-factor support (G-CSF) for neutropenia and prompt treatment of febrile neutropenia or infectious complications.

Clinical Implications

• Clinical Need: Metastatic TNBC remains an aggressive and difficult-to-treat breast cancer subtype, with historically limited treatment options.
• Biomarker-guided Recommendations: The updated guidelines distinguish treatment by PD-L1 status
  • Trodelvy monotherapy for PD-L1-negative disease
  • Trodelvy + pembrolizumab for PD-L1-positive tumors (Category 2A preferred option)
• Clinical Support: Category 1 represents the highest level of evidence and NCCN consensus, indicating strong clinical support for Trodelvy as a frontline treatment option in this population.
• “Backbone Treatment Option”: This update reflects emerging Phase 3 clinical trial evidence supporting the use of sacituzumab govitecan-based regimens earlier in the metastatic TNBC treatment pathway.
• Prescribing information: Available at accessdata.fda.gov.
• Side Effect Reporting: Patients are encouraged to report negative side effects to the FDA.

Sources:

1. “Trodelvy® Added as Preferred Regimen within First-Line Metastatic Triple-Negative Breast Cancer in NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®).” Gilead.com, 2026, www.gilead.com/company/company-statements/2026/trodelvy-added-as-preferred-regimen-within-first-line-metastatic-triple-negative-breast-cancer-in-nccn-clinical-practice-guidelines-in-oncology-nccn-guidelines. Accessed 9 Mar. 2026.
2. Cortés, Javier, et al. “Sacituzumab Govitecan in Untreated, Advanced Triple-Negative Breast Cancer.” New England Journal of Medicine, vol. 393, no. 19, 18 Oct. 2025, https://doi.org/10.1056/nejmoa2511734.
3. TRODELVY. Prescribing Information. Gilead Sciences, Inc.; March 2025.