Lynparza’s endometrial cancer first comes in the EU

EU approval for first-line endometrial cancer of AstraZeneca’s Imfinzi plus chemo – as well as of an Imfinzi plus Lynparza combo – means that European doctors will face a different treatment choice versus their US counterparts. In the US the battle is between Merck & Co’s Keytruda and GSK’s Jemperli, both of which are approved irrespective of patients’ mismatch repair (MMR) status. But the FDA refused to endorse Imfinzi plus Lynparza in MMR-proficient disease, in June backing Imfinzi plus chemo in MMR-deficient endometrial cancer only, based on a subgroup analysis of the Duo-E trial. The EMA, however, has gone with the CHMP recommendation to approve both this, and Imfinzi/chemo followed by the Imfinzi/Lynparza combo in MMR-proficient disease, even though the Duo-E result was clearly driven by MMR-deficient patients. To complicate matters further, Keytruda’s chemo combo isn’t available in any first-line endometrial cancer setting in the EU, and Merck appears not to be pursuing this use outside the US, where the FDA issued it a broad green light on the basis of the NCI-sponsored Keynote-868 trial. For its part, Jemperli has broad US approval, but the EMA has yet to decide on its use in first-line MMR-proficient endometrial cancer. How the first-line endometrial cancer dynamic has split MMR-deficientMMR-proficient USEUUSEUJemperli (GSK)Chemo combo, followed by monotherapy, approved based on RubyChemo combo, followed by monotherapy, approved based on RubyAccepted for review in Jun 2024, with decision expected in 2025Keytruda (Merck & Co)Chemo combo, followed by monotherapy, approved based on Keynote-868Not approvedChemo combo, followed by monotherapy, approved based on Keynote-868Not approvedImfinzi (AstraZeneca)Chemo combo, followed by monotherapy, approved based on Duo-ENot approvedChemo combo, followed by Lynparza combo, approved based on Duo-ESource: OncologyPipeline.