NCCN Updates Breast Cancer Guidelines: Sacituzumab Govitecan for 1L TNBC

The National Comprehensive Cancer Network (NCCN) has updated its Clinical Practice Guidelines in Oncology to include sacituzumab govitecan-hziy (Trodelvy) as a preferred first-line treatment option for patients with metastatic triple-negative breast cancer (TNBC).^1,2

The revised NCCN Guidelines (Version 1.2026) now list sacituzumab govitecan as a Category 1 preferred first-line therapy for patients with metastatic TNBC whose tumors are PD-L1 negative (combined positive score [CPS] <10) and who do not harbor germline BRCA1/2 pathogenic variants. Additionally, the guidelines now include the combination of sacituzumab govitecan and the PD-1 inhibitor pembrolizumab (Keytruda) as a Category 2A preferred option for first-line metastatic TNBC in patients with PD-L1-positive tumors (CPS ≥10).

Clinical Evidence from ASCENT-03 and ASCENT-04

These guideline updates are primarily supported by data from 2 pivotal phase 3 trials: ASCENT-03 (NCT05382299) and ASCENT-04 (NCT05382286).

In the ASCENT-03 study, sacituzumab govitecan monotherapy was evaluated against treatment of physician's choice in previously untreated patients with locally advanced or metastatic TNBC who were PD-L1–negative or not candidates for checkpoint inhibitors. Results demonstrated a statistically significant improvement in the primary end point of progression-free survival (PFS). The median PFS for patients receiving sacituzumab govitecan was 9.7 months compared with 6.9 months for those receiving physician’s choice of treatment (HR, 0.62; 95% CI, 0.50-0.77; P <.0001).²

The ASCENT-04 trial investigated the combination of sacituzumab govitecan and pembrolizumab vs the standard of care of pembrolizumab plus chemotherapy in the first-line PD-L1–positive setting. The combination arm reached a median PFS of 11.2 months compared with 7.8 months in the control arm, representing a 35% reduction in the risk of disease progression or death (HR, 0.65; 95% CI, 0.51-0.84; P =.0009).³

Addressing an Unmet Need in TNBC

TNBC is the most aggressive subtype of breast cancer, accounting for approximately 15% of all cases.⁵ It is characterized by the absence of estrogen and progesterone receptors and a lack of HER2 overexpression, leaving limited targeted treatment options. Historically, chemotherapy has been the backbone of first-line therapy, yet approximately 50% of patients with metastatic disease do not survive to receive second-line treatment.

Safety and Regulatory Status

The safety profile of sacituzumab govitecan in the first-line setting remains consistent with previous studies.¹ The most common adverse reactions (≥25%) include neutropenia, diarrhea, nausea, fatigue, and alopecia. The prescribing information includes a boxed warning for severe or life-threatening neutropenia and severe diarrhea.

While the NCCN has integrated these regimens into its clinical guidelines, the use of sacituzumab govitecan in the first-line setting remains investigational. Gilead Sciences has submitted supplemental biologics license applications to the US FDA and the European Medicines Agency for these indications.

REFERENCES

1. Trodelvy® added as preferred regimen within first-line metastatic triple-negative breast cancer in NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Gilead Sciences. January 28, 2026. Accessed January 29, 2026. https://tinyurl.com/4rjnahja

2. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer. Version 1.2026. National Comprehensive Cancer Network. Accessed January 29, 2026.

3. Cortés JC, Bardia A, Punie K, et al. Primary results from ASCENT-03: A randomized phase III study of sacituzumab govitecan (SG) vs chemotherapy (chemo) in patients (pts) with previously untreated advanced triple-negative breast cancer (TNBC) who are unable to receive PD-(L)1 inhibitors (PD-[L]1i). Presented at: 2025 ESMO Annual Congress; October 17-21, 2025; Berlin Germany. Abstract LBA20.

4. Tolaney SM, de Azambuja E, Kalinsky K, et al. Sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in previously untreated PD-L1–positive advanced triple-negative breast cancer (TNBC): Primary results from the randomized phase 3 ASCENT-04/KEYNOTE-D19 study. J Clin Oncol. 2025;43(suppl 17):LBA109. doi:10.1200/JCO.2025.43.17_suppl.LBA109

5. Triple-negative breast cancer. American Cancer Society. Accessed Janaury 29, 2026. https://tinyurl.com/55hwske7