The National Comprehensive Cancer Network (NCCN) updated their guidelines for breast cancer treatment indicating Datopotamab deruxtecan as category 2A, preferred in 1L TNBC

The National Comprehensive Cancer Network (NCCN) updated their guidelines for breast cancer treatment from Version 1.2026 to Version 2.2026

• Datopotamab deruxtecan (Dato-DXd, Datroway; TROP2-ADC) was changed to category 2A, preferred recommendation [previously category 2A, other recommended] in 1L TNBC PD-L1 CPS<10 and no germline BRCA1/2
  • results from the P3 TROPION-Breast02 trial were presented at ESMO 2025 where Dato-DXd demonstrated statistically significant improvement in mOS (23.7 vs 18.7 mos, HR: 0.79) and mPFS (10.8 vs 5.6 mos, HR 0.57) over chemotherapy in this indication
    • There has not yet been a peer-reviewed journal publication of TROPION-Breast02 results
  • FDA has accepted the sBLA for Dato-DXd and granted Priority Review for 1L mTNBC in patients who are not candidates for IO with PDUFA set for Jun 2, 2026
  • DS has also announced EU and JP filing of Dato-DXd in the same indication, with EU approval expected in Q3 2026 and JP expected approved in Q4 2026 / Q1 2027, based on standard assumptions
  • Trodelvy was previously added (Version 1.2026) as a category 1, preferred recommendation for the same indication in 1L TNBC PD-L1 CPS<10 and no germline BRCA1/2
• Trodelvy + pembrolizumab (Keytruda, pembro; anti–PD1) was changed to category 1, preferred recommendation [previously category 2A, preferred] in 1L TNBC PD-L1 CPS≥10
• NCCN inclusions prior to approvals of Dato-DXd and Trodelvy in 1L TNBC positions these therapies as clinically meaningful and potentially practice-changing, supporting accelerated uptake and reimbursement following approval
• Trodelvy being added to the NCCN guideline for both CPS<10 and CPS≥10 provides a potential backbone option for the broader 1L TNBC population, regardless of PD-L1 status
  • AZ/DS’ P3 TROPION-Breast05 evaluating Dato-DXd ± durvalumab (Imfinzi; anti-PD-L1) in 1L TNBC PD-L1+ CPS≥10 is ongoing with PCD of Jul 2027