NCCN Names Trodelvy a Preferred First-Line Treatment for Metastatic TNBC

The National Comprehensive Cancer Network (NCCN) has updated its clinical practice guidelines to include Trodelvy (sacituzumab govitecan-hziy) as a preferred first-line treatment option for patients with metastatic triple-negative breast cancer (TNBC), according to a news release from Gilead.

This update designates Trodelvy as a category 1 preferred first-line treatment for individuals whose disease is PD-L1–negative and who do not have a germline BRCA1/2 mutation. Category 1 is the highest-level recommendation provided by the NCCN. Additionally, the guidelines now include the combination of Trodelvy and the PD-1 inhibitor Keytruda (pembrolizumab) as a category 2A preferred option for patients with first-line metastatic TNBC whose tumors test positive for PD-L1. These changes aim to provide new pathways for patients facing an aggressive form of breast cancer that has historically seen limited treatment progress.

Main data that support the findings

The NCCN update is based on positive results from two phase 3 clinical studies known as ASCENT-03 and ASCENT-04. These trials evaluated the use of Trodelvy in the first-line setting, where patients have not yet received prior systemic therapies for metastatic disease. Historically, metastatic TNBC has been difficult to manage, with approximately 50% of patients not receiving any treatment beyond the first-line setting.

Trodelvy is a first-in-class Trop-2-directed antibody-drug conjugate. It works by targeting Trop-2, a cell surface antigen highly expressed in more than 90% of breast and lung cancers. The therapy is intentionally designed with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor payload. This unique combination delivers activity to both Trop-2 expressing cells and the tumor microenvironment through a bystander effect.

The updated guidelines distinguish between different patient profiles based on specific biomarkers. For patients with a PD-L1 score of less than 10 (CPS <10) and no germline BRCA1/2 mutations, Trodelvy is now a category 1 preferred option. For those with a PD-L1 score of 10 or higher (CPS ≥10), the combination with Keytruda is recognized as a category 2A preferred option. These updates validate the potential for the therapy to serve as a backbone treatment for patients with first-line metastatic TNBC.

Trial details

The foundational data for this guideline update come from the ASCENT-03 and ASCENT-04 phase 3 studies. These trials investigated the efficacy and safety of Trodelvy when used earlier in the treatment process than its currently approved indications. Gilead Sciences has submitted supplemental applications to the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for approval of Trodelvy in these indications based on these studies.

While these new studies focused on the first-line setting, Trodelvy is already approved in more than 60 countries for second-line or later metastatic TNBC. It is also approved in more than 50 countries for certain patients with pre-treated HR+/HER2- metastatic breast cancer. Currently, the therapy is being evaluated in multiple ongoing phase 3 trials across a range of tumor types with high Trop-2 expression, including lung and gynecologic cancers, as well as in curative settings.

Safety

The use of Trodelvy plus Keytruda in patients with first-line PD-L1+ metastatic TNBC, and Trodelvy as a monotherapy in patients with first-line metastatic TNBC who are not candidates for PD-1/PD-L1 inhibitors, are currently considered investigational. This means that while the NCCN has included them in the guidelines based on recent study results, the safety and efficacy of these specific uses have not yet been formally established by regulatory authorities.

In its currently approved uses, Trodelvy is indicated for adult patients with unresectable locally advanced or metastatic TNBC who have received two or more prior systemic therapies. It is also indicated for patients with HR-positive, HER2-negative metastatic breast cancer who have received endocrine-based therapy and at least two additional systemic therapies. Patients and caregivers are encouraged to discuss these updated NCCN recommendations with their medical teams to understand how the new category 1 and 2A statuses apply to their individual biomarker results.

References

1. “Trodelvy® Added as Preferred Regimen Within First-Line Metastatic Triple-Negative Breast Cancer in NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®),” by Gilead Sciences. News release; Feb. 4, 2026.

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI and reviewed by a human editor.

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