AZ gets landmark approval for Imfinzi/Lynparza combo

AstraZeneca has become the first company to get approval for the combination of an immunotherapy with a PARP inhibitor for treating endometrial cancer.

The European Commission has cleared AZ's PD-L1 inhibitor Imfinzi (durvalumab) alongside PARP inhibitor Lynparza (olaparib) for patients with primary advanced or recurrent endometrial cancer with mismatch repair proficient (pMMR) disease.

At the same time, Imfinzi on its own has been approved in the EU for patients with mismatch repair deficient (dMMR) disease, the same indication that was cleared by the FDA in June. There was, however, no word from the US regulator on the Imfinzi/Lynparza combination in pMMR.

Both the EC and FDA approvals draw on data from the DUO-E trial, published in the Journal of Clinical Oncology, which showed that the combination and Imfinzi alone extended the time to disease progression or death in previously untreated, advanced endometrial cancer patients when given on top of standard chemotherapy.

The Lynparza/Imfinzi regimen reduced that endpoint for patients with pMMR disease by 43% compared to the control arm, while Imfinzi cut it by 57% for the dMMR subjects.

"This approval is welcome news for patients with advanced or recurrent endometrial cancer in Europe, especially those with mismatch repair proficient disease who have limited options," commented DUO-E trial investigator Els Van Nieuwenhuysen, a gynaecological oncologist at the UZ Leuven in Belgium.

"The olaparib and durvalumab, as well as the durvalumab, regimens now have the potential to improve outcomes for all patients in this setting in Europe, regardless of mismatch repair status," she added.

Endometrial cancer is the fourth most common cancer in women in Europe and, according to AZ, there is a significant need for new treatment options for pMMR disease in particular, which makes up around 70%-80% of all cases. There are around 417,000 cases diagnosed each year, according to 2020 figures from World Cancer Research Fund International, and the cancer killed around 97,000 women in the same year.

The new approval bolsters AZ's position in what is becoming a battle with GSK and MSD in first-line endometrial cancer, with Imfinzi and Imfinzi/Lynparza pitted against the GSK's Jemperli (dostarlimab) and MSD's Keytruda (pembrolizumab) in this space.

Originally cleared only for dMMR tumours, earlier this month a Jemperli chemo regimen got the go-ahead for all patients with endometrial cancer, regardless of MMR status, based on the RUBY trial results, which were the first to show an overall survival benefit for a cancer immunotherapy in this setting.

The RUBY data is also under review in the EU, having been filed in June, while a second part of the study is also looking at the combination of Jemperli with GSK's PARP drug Zejula (niraparib).

Keytruda, meanwhile, was cleared by the FDA in June for first-line endometrial cancer therapy alongside chemo earlier this year, based on progression-free survival data from the NRG-GY018 study, also without any MMR restrictions on the label.

AZ said that regulatory submissions for Imfinzi and Lynparza are currently under review in Japan and several other countries based on the DUO-E trial.