Lynparza, Imfinzi combo recommended for nod in EU by CHMP for endometrial cancer: AstraZeneca
Cambridge: AstraZeneca has announced that Imfinzi (durvalumab) and Lynparza (olaparib) have been recommended for approval in the European Union (EU) as treatment for certain patients with primary advanced or recurrent endometrial cancer. Imfinzi plus chemotherapy as 1st-line treatment followed by Lynparza and Imfinzi has been recommended for patients with mismatch repair proficient (pMMR) disease. Imfinzi plus chemotherapy followed by Imfinzi alone has been recommended for patients with mismatch repair deficient (dMMR) disease.
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based its positive opinion on a prespecified exploratory subgroup analysis by mismatch repair (MMR) status from the DUO-E Phase III trial, which was published in the Journal of Clinical Oncology in October 2023.
This analysis showed a reduction in the risk of disease progression or death for pMMR patients in the Lynparza and Imfinzi arm by 43% (median 15.0 months versus 9.7 months, hazard ratio [HR] 0.57; 95% confidence interval [CI] 0.44-0.73) versus the control arm. Results for dMMR patients showed a reduction in the risk of disease progression or death in the Imfinzi arm by 58% (median not reached versus 7.0 months, HR 0.42; 95% CI 0.22-0.80) versus the control arm.
In Europe, endometrial cancer is the fourth most common cancer in women, with nearly 125,000 diagnoses and more than 30,000 deaths in 2022. Patients diagnosed at an early stage of disease have a five-year survival rate of approximately 80-90%, but that falls to less than 20% for people with advanced disease. There is a significant need for new treatment options, especially for the 70-80% of patients with pMMR disease. This recommendation underscores the importance of MMR testing at point of diagnosis, which is well established and widely available.
Els Van Nieuwenhuysen, Gynaecological Oncologist at the UZ Leuven, Belgium and trial investigator, said, “Patients with advanced or recurrent endometrial cancer currently have a very poor prognosis, especially those with mismatch repair proficient disease. This recommendation underscores the significant benefit shown with durvalumab as well as with the olaparib and durvalumab combination for patients with both mismatch repair deficient and mismatch repair proficient status. This marks an important step toward improving outcomes for these patients in Europe.”
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said, “The recommendation for approval in the EU recognises the potential of the Lynparza and Imfinzi combination to provide clinical benefit for patients with endometrial cancer, especially for those with mismatch repair proficient disease who have few available treatments today. If approved, patients in Europe will have a new option for combination treatment that brings the additional benefit of PARP inhibition to immunotherapy.”
The safety profiles of both experimental regimens were manageable, well-tolerated and broadly consistent with the known profiles of the individual agents.
Regulatory submissions for Imfinzi and Lynparza are currently under review in Japan and several other countries based on the DUO-E trial. Imfinzi plus chemotherapy was recently approved for dMMR patients with primary advanced or recurrent endometrial cancer in the US.
