Dato sees double survival trouble

AstraZeneca and Daiichi Sankyo now have two survival-related problems involving their anti-TROP2 ADC datopotamab deruxtecan. The companies today said final OS analysis of the Tropion-Breast01 trial, in second-line ER-positive HER2-negative breast cancer, had failed to yield a statistically significant result versus chemo; PFS from the study hit statistical significance at last year’s ESMO, but interim OS showed a non-significant 0.84 hazard ratio. At that time OS was said to favour dato-dxd numerically – wording that was omitted from today’s statement. Dato-dxd’s first problem is in second-line NSCLC, where the supporting Tropion-Lung01 trial failed in all-comers, resulting in the companies filing only for patients with non-squamous histology. However, this too is backed only by a PFS benefit, with final OS data at this month’s World Conference on Lung Cancer showing a non-significant 2.1-month benefit. In breast cancer at least the companies might argue that subsequent therapy – with Gilead’s Trodelvy or perhaps even with Enhertu – might have rescued patients progressing on chemo control, but it’s notable that Trodelvy’s US approval is backed by PFS as well as OS benefits. The FDA is due to review dato-dxd’s lung and breast cancer filings within the next six months. 

Datopotamab deruxtecan's two registrational trials

Notes: *mOS in all-comers was 12.9mth vs 11.8mth (HR=0.94, p=0.530); **at ESMO 2023 interim OS was described as numerically favourable (HR=0.84). Source: OncologyPipeline.