Results of AstraZeneca’s Duo-E study in endometrial cancer have given rise to another difference of opinion between the FDA and its European counterpart. On Friday the EU’s CHMP recommended approval of Imfinzi combined with chemo and Lynparza in first-line endometrial cancer patients whose disease was mismatch repair proficient (pMMR) – a setting based on Duo-E that the FDA last month refused to endorse. What the US regulator did approve was Imfinzi plus chemo, only in mismatch repair-deficient (dMMR) endometrial cancer; that came after Duo-E showed a PFS benefit favouring both the Lynparza containing and non-containing cohorts, an effect apparently driven by dMMR patients, who comprised only some 20% of Duo-E’s roughly 700-strong population. A subgroup analysis based on dMMR no longer showed Lynparza adding a benefit over Imfinzi plus chemo alone. The CHMP has also endorsed Imfinzi plus chemo in dMMR patients, meaning that in the EU Astra will be able to treat a broad spectrum of first-line endometrial cancers. The US restriction to dMMR disease means that Astra has fallen behind Merck & Co, whose Keytruda was approved irrespective of MMR status; GSK's Jemperli faces a 23 August PDUFA date for use in all-comers. Duo-E trial subgroup analyses by patients’ MMR status Arm BArm A (control)Arm C Imfinzi + chemo, then ImfinziChemo, then placeboImfinzi + chemo, then Imfinzi + LynparzamPFS in dMMR (n=143)NR7.0mth31.8mthHR=0.42––HR=0.41US approved 17 Jun 2024Positive CHMP 28 Jun 2024–Not approvedmPFS in pMMR (n=575)9.9mth9.7mth15.0mthHR=0.77––HR=0.57Not approved–Positive CHMP 28 Jun 2024Not US approvedSource: Journal of Clinical Oncology & OncologyPipeline.
Results of AstraZeneca’s Duo-E study in endometrial cancer have given rise to another difference of opinion between the FDA and its European counterpart. On Friday the EU’s CHMP recommended approval of Imfinzi combined with chemo and Lynparza in first-line endometrial cancer patients whose disease was mismatch repair proficient (pMMR) – a setting based on Duo-E that the FDA last month refused to endorse. What the US regulator did approve was Imfinzi plus chemo, only in mismatch repair-deficient (dMMR) endometrial cancer; that came after Duo-E showed a PFS benefit favouring both the Lynparza containing and non-containing cohorts, an effect apparently driven by dMMR patients, who comprised only some 20% of Duo-E’s roughly 700-strong population. A subgroup analysis based on dMMR no longer showed Lynparza adding a benefit over Imfinzi plus chemo alone. The CHMP has also endorsed Imfinzi plus chemo in dMMR patients, meaning that in the EU Astra will be able to treat a broad spectrum of first-line endometrial cancers. The US restriction to dMMR disease means that Astra has fallen behind Merck & Co, whose Keytruda was approved irrespective of MMR status; GSK's Jemperli faces a 23 August PDUFA date for use in all-comers.
Duo-E trial subgroup analyses by patients’ MMR status
| | Arm B | Arm A (control) | Arm C |
|---|
| | Imfinzi + chemo, then Imfinzi | Chemo, then placebo | Imfinzi + chemo, then Imfinzi + Lynparza |
| mPFS in dMMR (n=143) | NR | 7.0mth | 31.8mth |
| HR=0.42 | – |
| – | HR=0.41 |
US approved 17 Jun 2024
Positive CHMP 28 Jun 2024 | – | Not approved |
| mPFS in pMMR (n=575) | 9.9mth | 9.7mth | 15.0mth |
| HR=0.77 | – |
| – | HR=0.57 |
| Not approved | – | Positive CHMP 28 Jun 2024
Not US approved |
