Phase 3 study TROPION-Breast02 of datopotamab deruxtecan (Datroway, Dato-DXd) in 1L PD-L1- TNBC supports the potential to become the new standard of care in first line triple negative breast cancer patients non eligible for immunotherapy

On Oct 20^th, 2025, AstraZeneca hosted its ESMO IR Event (webcast, presentation, brochure, biographies) where the company discussed key ESMO 2025 presentations including TROPION-Breast02

• AZ reiterated that the P3 TROPION-Breast02 of datopotamab deruxtecan (Datroway, Dato-DXd; TOP2-ADC) in 1L PD-L1- TNBC demonstrated statistically significant and clinically meaningful benefit across the dual primary endpoints of PFS and OS
  • It was noted that the survival curves separated early and remained apart throughout follow-up, indicating a durable treatment effect
  • The ~5 mos improvement in OS benefit was quoted to be clinically meaningful, particularly for younger TNBC patients with aggressive disease
• AZ noted that there were no new safety signals from the TROPION-Breast02 trial and added that the number of SAEs were “very similar” between the Dato-DXd arm and the chemotherapy arm
  • Although there were more dose reductions and delays in the Dato-DXd arm, more patients on chemotherapy discontinued treatment altogether
  • While Dato-DXd was associated with dry eyes, stomatitis and nausea, chemotherapy arm had more myelosuppressive AEs, highlighting Dato-DXd’s potential to become the new SoC for 1L
  • Dr. Dent noted that ILD/pneumonitis events were rare in both arms, which was “very reassuring”
  • The speaker noted that, unlike Trodelvy in ASCENT-03, no drug-related deaths were observed in TROPION-Breast02, with mucositis and ocular events being the main adverse events
    • She noted that mucositis and ocular events were generally mild; approximately 90% of mucositis cases resolved by the data cut-off and no discontinuations occurred
    • Most ocular events were dry eye and over 70% resolved following dose reductions
  • She also emphasized reduced “time toxicity” with Dato-DXd
    • Dato-DXd infusions are ~90 minutes for the first dose and ~30 minutes thereafter, vs 4–5 hours first and ~2 hours subsequently with some other ADCs, an efficiency that “makes a real difference,” especially for patients on therapy >1 year
• Dr. Dent indicated that Dato-DXd is expected to be included in the NCCN guidelines “in the next six months”, and noted her excitement about being able to use Dato-DXd in the clinic “very soon”
• Dr. Dent clarified that efficacy was “very consistent” across geographies for PFS, OS, and DoR, and that the OS differences observed in the US/EU/Canada subgroup came from a post-hoc analysis
  • The US subgroup results were “very similar” to ITT population, while the EU subset will be examined further
  • She also noted that around 20% of patients were early relapsers (15% within six months), which is “really important” clinically since most TNBC relapses occur early
    • This reinforces Dato-DXd’s activity, including potential CNS activity consistent with TUXEDO-2 data
  • Dr. Dent emphasized that the “more than doubling” of both response rate and duration of response was “really quite profound,” viewing Dato-DXd as a “more efficacious compound” than Trodelvy
  • While therapy choice may depend on toxicity, she noted that Trodelvy is “a little bit more challenging” due to myelosuppression, whereas Dato-DXd appears easier to deliver
• The speaker explained that although TROPION-Breast02 did not allow crossover, around 75% of patients in each arm received subsequent therapy, including non-TROP2 ADCs
  • Because many patients never reach 2L therapy, the OS benefit observed is “really important”
  • They added that crossover design choices are a key drug development consideration, as they influence endpoint interpretation, regulatory review, reimbursement, and market access

On Oct 21^st, 2025, Daiichi Sankyo (DS) hosted its ESMO IR Event (webcast, presentation) where the company discussed key ESMO 2025 presentations, including TROPION-Breast02

• DS messaged the statistically significant and clinical meaningful improvement of dual primary endpoints of PFS and OS in P3 TROPION-Breast02  supports the use of Dato-DXd as the new SoC for 1L TNBC for whom IO is not an option 
  • OS differences observed in the US/Canada subgroup were based on small sample sizes, limiting their statistical robustness
• Management clarified that while TROPION-Breast02 did not permit crossover, approximately 30% of control-arm patients received subsequent therapies post-progression, including other ADCs
• In response to a question comparing Dato-DXd with Trodelvy, DS stated that although no head-to-head data are available, Dato-DXd is believed to perform better due to its stable linker technology

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