Astra completes its defeat of Roche in AKT

Roche and AstraZeneca’s fortunes in AKT inhibition diverged some time ago, and today Astra completed its rout. The UK company’s US approval for capivasertib, trademarked Truqap, has come a year after Roche pulled the plug on its rival, ipatasertib. Even so the victory hasn’t been as comprehensive as might have been expected: the FDA has restricted Truqap’s label, in second-line ER-positive HER2-negative breast cancer, to patients with PIK3CA/AKT1/PTEN alterations, effectively cutting the addressable population in half. This is despite Truqap plus Faslodex meeting both primary PFS endpoints of the CAPItello-291 study, cutting risk of progression or death versus Faslodex alone by 40% in all-comers and by 50% in the PIK3CA/AKT1/PTEN-altered subgroup. In ER-positive HER2-negative breast cancer Roche’s ipatasertib was tested in front-line settings, and failed Ipatunity-130, a study in PIK3CA/AKT1/PTEN-altered disease. Ipatunity-150, an Ibrance/Faslodex combo study, was completed without data being reported, and Roche finally discontinued ipatasertib after its failure in prostate cancer. Truqap’s next test comes in first-line triple-negative breast cancer, with data due next year from CAPItello-290; scoring in this trial could be tougher than in CAPItello-291, since it tests overall survival, doesn’t preselect for PIK3CA/AKT1/PTEN, and doesn’t include immunotherapy, an emerging treatment standard.

A comparison of two AKT inhibitors

Note: *also had TNBC cohort. Source: OncologyPipeline.

This story has been amended to correct the hazard ratio in CAPItello-291.