Breast Cancer NCCN Guidelines Update (Version 3.2026): Datopotamab deruxtecan (Dato-DXd, Datroway) was upgraded to Category 1, preferred recommendation

The National Comprehensive Cancer Network (NCCN) updated their guidelines for breast cancer treatment from Version 2.2026 to Version 3.2026

• Datopotamab deruxtecan (Dato-DXd, Datroway; TROP2-ADC) was upgraded to Category 1, preferred recommendation [previously Category 2A, preferred] in 1L TNBC PD-L1 CPS<10 and no germline BRCA1/2
  • The Category 1 upgrade was likely supported by the peer-reviewed publication of P3 TROPION-Breast02 trial results in Annals of Onc. (IF: ~51) on Apr 3, 2026
    • Dato-DXd met its dual primary endpoints of OS (23.7 vs 18.7 mos; HR: 0.79) and PFS (10.8 vs 5.6 mos; HR: 0.57) vs CT in the TB-02 trial in 1L mTNBC patients ineligible for anti-PD-(L)1 therapy
  • FDA approved Dato-DXd in 1L mTNBC (non-IO candidates), while CHMP Type II Variation review is also ongoing
• This is the third update for Dato-DXd in this setting in 2026:
  • Jan 16, 2026 (ver1.2026): category 2A, other recommended
  • Feb 27, 2026 (ver2.2026): category 2A, preferred
  • May 8, 2026 (ver3.2026): category 1, preferred
• Dato-DXd's Category 1, preferred upgrade creates NCCN parity with Trodelvy in 1L mTNBC PD-L1 CPS<10 with no germline BRCA1/2, which is also Category 1, preferred supported by data from P3 ASCENT-03 trial
• Trodelvy maintains a key advantage through its NCCN Category 1 guideline presence across both CPS<10 and CPS≥10 mTNBC, supported by positive results from P3 ASCENT-04/03 trials, positioning Trodelvy as a 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 data readout expected in H1 2027