Updated NCCN Guidelines Recommend First-Line Sacituzumab Govitecan–Based Regimens for TNBC

The National Comprehensive Cancer Network (NCCN) has updated its Clinical Practice Guidelines in Oncology for breast cancer to categorize sacituzumab govitecan-hziy (Trodelvy) as a category 1 preferred regimen for the first-line treatment of patients with metastatic triple-negative breast cancer (mTNBC) whose disease is PD-L1 negative (defined as a combined positive score [CPS] of < 10) and has no germline BRCA1/2 pathogenic variants.^1,2

The guidelines were also updated to include sacituzumab govitecan plus pembrolizumab (Keytruda) as a category 1 preferred first-line regimen for patients with mTNBC whose disease is PD-L1 positive (defined as a CPS of ≥ 10). Notably, the combination was previously included in the guidelines as a category 2A preferred regimen for this patient population.

These guideline updates were supported by data from the phase 3 ASCENT-03 (NCT05382299) and ASCENT-04 (NCT05382286) trials for sacituzumab govitecan monotherapy and sacituzumab govitecan plus pembrolizumab, respectively. In ASCENT-03, treatment with sacituzumab govitecan (n = 279) led to a median progression-free survival (PFS) of 9.7 months (95% CI, 8.1-11.1) vs 6.9 months (95% CI, 5.6-8.2) with chemotherapy (n = 279; HR, 0.62; 95% CI, 0.50-0.77; P < .001).³ In ASCENT-04, patients who received sacituzumab govitecan plus pembrolizumab (n = 221) achieved a median PFS of 11.2 months (95% CI, 9.3-16.7) vs 7.8 months (95% CI, 7.3-9.3) among those who received pembrolizumab plus chemotherapy (n = 222; HR, 0.65; 95% CI, 0.51-0.84; 2-sided P < .001).⁴

Based on these data sets, supplemental applications seeking the approval of sacituzumab govitecan monotherapy and sacituzumab govitecan plus pembrolizumab in their respective indications have been submitted to the FDA and the European Medicines Agency.¹

“For the [past] 20 years, there has been limited meaningful progress to treat [patients] with first-line mTNBC,” Mika Kakefuda Derynck, MD, senior vice president and head of the Oncology Therapeutic Area at Gilead Sciences, said in a news release. “These updated guidelines validate the potential for [sacituzumab govitecan] to become a backbone treatment option for [patients with] first-line mTNBC.”

What additional findings were seen in ASCENT-03?

This international, open-label trial randomly assigned patients to receive sacituzumab govitecan at 10 mg/kg on days 1 and 8 of 21-day cycles or physician’s choice of chemotherapy.³ The primary end point was PFS. Secondary end points were overall survival (OS), overall response rate (ORR), duration of response (DOR), time to response (TTR), safety, and quality of life.

The ORR in the sacituzumab govitecan arm was 48% (95% CI, 42%-54%) vs 46% (95% CI, 40%-52%) in the chemotherapy arm (stratified OR, 1.1; 95% CI, 0.8-1.6). Additionally, the median TTR was 1.6 months in both the sacituzumab govitecan (95% CI, 0.7-16.7) and chemotherapy (95% CI, 0.9-6.8) arms. Although OS data were not mature at the time of the data presentation, the median OS was 21.5 months (95% CI, 17.7-not reached [NR]) with sacituzumab govitecan vs 20.2 months (95% CI, 18.2-NR) with chemotherapy (HR, 0.98; 95% CI, 0.75-1.30).

Regarding safety, grade 3 or higher treatment-related adverse effects (AEs) were reported in 61% vs 53% of patients in the sacituzumab govitecan vs chemotherapy arms, respectively. Treatment-emergent AEs (TEAEs) led to treatment discontinuation in 10 vs 33 patients in these respective arms. TEAEs led to death in 7 patients who received sacituzumab govitecan vs 1 who received chemotherapy.

What were notable additional findings from ASCENT-04?

This open-label, international trial randomly assigned patients 1:1 to receive sacituzumab govitecan at 10 mg/kg on days 1 and 8 plus pembrolizumab at 200 mg on day 1 of each 21-day cycle, or pembrolizumab at the same dose and schedule plus chemotherapy of physician’s choice.⁴ PFS served as the primary end point. Secondary end points included OS, ORR, DOR, and safety.

The ORR was 60% (95% CI, 53%-66%) in the sacituzumab govitecan arm vs 53% (95% CI, 46%-60%) in the chemotherapy arm (OR, 1.3; 95% CI, 0.9-1.9). The respective median DORs were 16.5 months (95% CI, 12.7-19.5) and 9.2 months (95% CI, 7.6-11.3). OS data were not mature at the time of this analysis.

Regarding safety, 71% of patients in the sacituzumab govitecan arm experienced grade 3 or higher AEs vs 70% of those in the chemotherapy arm. Treatment discontinuation due to AEs occurred in 12% vs 31% of patients in these respective arms. AEs led to death in 3% of patients in each arm.

References

1. Trodelvy added as preferred regimen within first-line metastatic triple-negative breast cancer in NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines). News release. Gilead Sciences. January 28, 2026. Updated February 27, 2026. Accessed March 17, 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
2. NCCN. Clinical Practice Guidelines in Oncology. Breast cancer, version 2.2026. Accessed March 17, 2026. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf
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). Ann Oncol. 2025;36(suppl 2):S1565-S1566. doi:10.1016/j.annonc.2025.09.030
4. Tolaney SM, de Azambuja E, Kalinsky K, et al. Sacituzumab govitecan plus pembrolizumab for advanced triple-negative breast cancer. N Engl J Med. 2026;394(4):354-366. doi:10.1056/NEJMoa2508959