NCCN Adds Trodelvy as Preferred First-Line Option in Metastatic Triple-Negative Breast Cancer

Key Clinical Summary

• National Comprehensive Cancer Network (NCCN) Guidelines update adds Trodelvy as a category 1 preferred first-line treatment for programmed cell death ligand 1 (PD-L1)–negative metastatic triple-negative breast cancer (TNBC) without germline BRCA1/2 pathogenic variants.
• Trodelvy plus pembrolizumab is included as a category 2A preferred first-line option for PD-L1–positive (CPS ≥ 10) metastatic TNBC.
• Recommendations are based on phase 3 ASCENT-03 and ASCENT-04 trial results; regulatory submissions are under review in the US and Europe.

The NCCN has updated its Clinical Practice Guidelines in Oncology to include Trodelvy (sacituzumab govitecan-hziy) in first-line metastatic TNBC. Announced January 28, 2026, the update reflects evidence from Gilead Sciences’ phase 3 ASCENT-03 and ASCENT-04 trials and positions Trodelvy across PD-L1–defined patient subsets. Based on these findings, Gilead has submitted supplemental applications to both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) seeking approval for these indications.

The NCCN Guidelines now list Trodelvy as a category 1 preferred first-line treatment for people with metastatic TNBC that is PD-L1 negative (CPS < 10) and without germline BRCA1/2 pathogenic variants. In addition, the guidelines include Trodelvy in combination with pembrolizumab (Keytruda) as a category 2A preferred option for first-line metastatic TNBC with PD-L1–positive tumors (CPS ≥ 10).

Metastatic TNBC remains the most aggressive breast cancer subtype and has historically been difficult to treat. Despite recent advances, approximately 50% of patients do not receive therapy beyond first line, underscoring the need for effective options earlier in the disease course. The guidelines acknowledge distinct treatment pathways based on PD-L1 status, including use of Trodelvy monotherapy for patients who are not candidates for PD-1/PD-L1 inhibitors.

The use of Trodelvy plus pembrolizumab in first-line PD-L1–positive metastatic TNBC and Trodelvy monotherapy in first-line settings for patients ineligible for PD-1/PD-L1 inhibitors are investigational, and safety and efficacy have not been established.

Clinical Implications

For oncology leaders, clinicians, and pathway stakeholders, the NCCN update represents a meaningful shift in first-line metastatic TNBC management. A category 1 preferred designation for Trodelvy in PD-L1–negative disease may influence clinical pathways, coverage decisions, and sequencing strategies, particularly given the high risk of rapid progression in this population.

The inclusion of a PD-L1–stratified approach aligns treatment selection with biomarker status and reflects evolving standards of care. From a payer and pathway perspective, earlier access to a preferred option may reduce attrition between lines of therapy—an important consideration given that half of patients do not reach second line.

The submissions to the FDA and EMA signal potential near-term regulatory decisions that could further formalize Trodelvy’s role in first-line metastatic TNBC across geographies. As evidence matures, these recommendations may serve as a foundation for broader adoption and ongoing evaluation in earlier treatment settings.

Conclusion

The NCCN’s latest update elevates Trodelvy into preferred first-line use for metastatic TNBC, with recommendations tailored by PD-L1 status. Backed by phase 3 evidence and pending regulatory review, the change may reshape clinical pathways and access decisions in this high-need population.

Reference

Trodelvy® added as preferred regimen within first-line metastatic triple-negative breast cancer in NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Gilead. Press Release. January 28, 2026. Accessed February 4, 2026. https://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