Breast Cancer NCCN Guidelines Update

On January 16, 2026 The National Comprehensive Cancer Network (NCCN) updated their guidelines for breast cancer treatment from Version 5.2025 to Version 1.2026. The following updates were made for 1L TNBC.

• 1L TNBC PD-L1 CPS<10 and no germline BRCA1/2:
  • Datopotamab deruxtecan (Dato-DXd, Datroway; TROP2-ADC) was added as a category 2A, other recommended 
    • Recall, results from the P3 TROPION-Breast02 trial were presented at ESMO 2025 where Dato-DXd demonstrated statistically significant improvement in OS (23.7 vs 18.7 mos, HR: 0.79) and PFS (10.8 vs 5.6 mos, HR 0.57) over chemotherapy in this patient population
    • Results from Dato-DXd in 1L TNBC PD-L1 CPS<10 (TROPION-Breast-02) have not yet been published in a peer-reviewed journal
    • US approval for Dato-DXd in 1L TNBC ineligible for anti-PD-(L)1 is expected in Q2-Q3 2026, however DS and AZ have not publicly disclosed an FDA filing
    • Note, DS has announced EU filing of Dato-DXd in the same indication, with EU approval expected in Q3 2026, based on standard assumptions
  • Note, Trodelvy was added as a category 1, preferred recommendation for the same indication
    • Results for Trodelvy in 1L TNBC PD-L1 CPS<10 (ASCENT-03) was published in The New England Journal of Medicine in Oct 2025
  • The discussion section has not been updated since June 7, 2024; therefore, the rationale for the differing category assignments between Trodelvy and Dato‑DXd is unclear, potentially due to manuscript availability
• 1L TNBC PD-L1 CPS≥10 and no germline BRCA1/2:
  • Trodelvy + pembrolizumab (Keytruda, pembro; anti–PD1) was added as a category 2A, preferred recommendation
    • Results for Trodelvy in 1L TNBC PD-L1 CPS≥10 (ASCENT-04) have not yet been published and are expected in Q1 2026