Excess of solid cancers after prasugrel: The food and drug administration outlook

The TRITON-TIMI 38 was a head-to-head trial to assess the efficacy and safety of the experimental antiplatelet agent prasugrel versus standard care with clopidogrel on top of aspirin. Besides some early ischemic protection at the expense of growing over time overwhelming bleeding disadvantage, prasugrel-treated patients experienced significantly higher cancer rates. Recently, the Food and Drug Administration (FDA) issued a Prasugrel Second Review, a detailed 357-page document presenting realistic outlook on various aspects of the TRITON trial including distributions of different cancers between treatment arms. The comprehensive FDA analysis revealed that some preclinical but especially human data overwhelmingly indicate excessive cancer risks after prasugrel. Indeed, despite excellent baseline balance, prasugrel-treated patients experienced extra cancer-related deaths, 27% higher risks for new cancers occurrences, and 36.8% increase of new solid malignant cancers. The FDA report concluded that cancer risks after prasugrel are real, especially high in women, and after 4 months of therapy at least for solid highly metastatic cancers. These unexpected findings may be explained by disruption of tumor-platelet aggregates by chronic profound oral platelet inhibition causing extensive dissemination of initially silent tumors. Since prasugrel gained regulatory approval, the alarming cancer data should be confirmed in further specifically designed trial and carefully assessed in large registries.