ASCENT-04: Biomarker Analysis Favors Sacituzumab Govitecan in 1L TNBC

New data from the phase 3 ASCENT-04 trial, presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, reinforce the efficacy of sacituzumab govitecan (SG, Trodelvy) combined with pembrolizumab (Keytruda) as a potential first-line standard of care for patients with previously untreated, PD-L1–positive metastatic triple-negative breast cancer (mTNBC).

The exploratory analysis, presented by Sara M. Tolaney, MD, MPH, FASCO, of the Dana-Farber Cancer Institute, demonstrated that the progression-free survival (PFS) benefit of the SG-pembrolizumab combination persisted across key biomarker subgroups, including Trop-2 expression levels, germline and somatic BRCA1/2 mutation status, and HER2 expression levels.

A broad benefit across Trop-2 expression

Sacituzumab govitecan is an antibody-drug conjugate (ADC) targeting Trop-2, a surface protein frequently overexpressed in TNBC. In this prespecified retrospective exploratory analysis, investigators sought to determine if the level of Trop-2 expression impacted the efficacy of the combination therapy.

Participants were grouped by Trop-2 expression quartiles based on H-scores determined by immunohistochemistry (IHC). The findings indicated that median PFS (mPFS) was longer for those receiving SG plus pembrolizumab compared to chemotherapy plus pembrolizumab across all quartiles:

• Q1 (Lowest expression): 9.3 months vs 9.0 months (HR, 0.81)
• Q2: 9.6 months vs 7.4 months (HR, 0.73)
• Q3: 13.5 months vs 8.4 months (HR, 0.46)
• Q4 (Highest expression): 16.6 months vs 9.2 months (HR, 0.57)

While the data showed a trend toward greater separation of Kaplan-Meier curves in the higher expression quartiles (Q3 and Q4), the benefit remained consistent across the entire biomarker analysis set.

Efficacy independent of BRCA and HER2 status

The study also evaluated the impact of tumor BRCA (tBRCA) mutations and HER2 expression, factors known to influence the efficacy of certain mTNBC treatments. Using whole exome sequencing (WES), researchers identified that 23% of participants in the SG group and 20% in the chemotherapy group had tBRCA mutations.

The mPFS was longer with the SG combination regardless of tBRCA status. In the tBRCA wild-type (WT) subgroup, mPFS was 9.6 months with SG vs 7.4 months with chemotherapy (HR, 0.67). In the tBRCA mutated subgroup, mPFS reached 16.6 months with SG vs 12.9 months with chemotherapy (HR, 0.88).

Similarly, the benefit of SG plus pembrolizumab was observed across HER2 subgroups. In patients classified as HER2 IHC 0, the mPFS was 16.6 months for the SG arm vs 9.0 months for chemotherapy (HR, 0.69). For those with HER2-low status (IHC 1+ or IHC 2+/ISH-), mPFS was 11.2 months vs 7.7 months, respectively (HR, 0.67).

Implications for oncology nursing

For oncology nurses, these findings provide critical context for patient education and treatment expectations. The primary ASCENT-04 analysis previously established a significant improvement in PFS for the SG plus pembrolizumab arm (HR, 0.65; P < .001). This subgroup analysis further confirms that patients may benefit from this ADC-immunotherapy combination regardless of their specific biomarker profile, simplifying the decision-making process for first-line therapy in PD-L1–positive disease.

However, Tolaney noted that because many subgroup sample sizes were small and the analyses were descriptive, caution should be used when interpreting these specific results.

Reference

1. Tolaney SM, Schmid P, de Azambuja E, et al. ASCENT-04: Analysis of efficacy by biomarker subgroups with sacituzumab govitecan + pembrolizumab vs chemotherapy + pembrolizumab in participants with previously untreated PD-L1+ metastatic triple-negative breast cancer. Presented at: 2026 ASCO Annual Meeting; May 29-June 2, 2026; Chicago, IL.