New Combination Drug for Endometrial Cancer Approved in EU

The European Commission has approved a combination of an immunotherapy agent with a poly (ADP-ribose) polymerase (PARP) inhibitor for the treatment of certain patients with primary advanced or recurrent endometrial cancer.

Imfinzi (durvalumab, AstraZeneca) plus chemotherapy as a first-line treatment followed by Lynparza (olaparib, AstraZeneca) plus Imfinzi was approved for patients with mismatch repair proficient (pMMR) disease.

Imfinzi plus chemotherapy followed by Imfinzi alone was approved for patients with mismatch repair deficient (dMMR) disease.

Most patients with endometrial cancer are diagnosed at an early stage when the cancer is confined to the uterus and have a 5-year survival rate of 80%-90%with surgical and/or radiation treatment. 

However, this falls to less than 20% among women with advanced disease (stage III-IV), of whom, 70%-80% have pMMR disease, and 20%-30% have dMMR disease. There is a significant need for new treatment options, especially for those with dMMR disease, and combined immunotherapy plus chemotherapy is emerging as a new standard of care for these patients.

Broad Development Program in Multiple Tumor Types

Across Europe, nearly 125,000 women were diagnosed with endometrial cancer in 2022. Durvalumab, approved as immunotherapy for some cases of unresectable non-small cell lung cancer, is a human monoclonal antibody that binds to the PD-L1 protein and blocks its interaction with PD-1 and CD80 proteins, countering the tumor’s inhibition of immune responses. More than 220,000 patients have now been treated with durvalumab, which is being tested as solo and combination treatment for a variety of solid tumors, including small cell and non–small cell lung cancers, breast, bladder, and several gastrointestinal and gynecologic cancers.

Olaparib is a first-in-class PARP inhibitor that is the first to specifically target the DNA damage response in various types of tumors to promote cancer cell death. It may also help enhance immunogenicity and increase the impact of anti-tumor immune responses. It is currently approved in several countries across multiple tumor types, including ovarian, breast, pancreatic, and prostate cancers, and has now been used in treatment for about 140,000 patients worldwide. It is being jointly developed by AstraZeneca and MSD, both as a monotherapy and in combination with other potential agents.

Endometrial Cancer Progression-Free Survival Enhanced

The approval of durvalumab plus olaparib in endometrial cancer by the European Commission followed a positive opinion last month from the Committee for Medicinal Products for Human Use of the European Medicines Agency. Approval was based on a prespecified exploratory subgroup analysis by MMR status of the phase 3 DUO-E trial, published in the Journal of Clinical Oncology in October 2023. 

This demonstrated that carboplatin-paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib yielded a statistically significant and clinically meaningful progression-free survival benefit in patients with advanced or recurrent endometrial cancer. In patients with pMMR disease, the dual durvalumab plus olaparib regimen reduced the risk for disease progression or death by 43% (median, 15.0 months vs 9.7 months; hazard ratio [HR], 0.57; 95% CI, 0.44-0.73) vs the control arm.

In patients with dMMR disease, the durvalumab regimen reduced the risk for disease progression or death by 58% (median, not reached vs 7.0 months; HR, 0.42; 95% CI, 0.22-0.80) vs the control arm.

Trial investigator, Prof Dr Els Van Nieuwenhuysen, a gynecological oncologist at University Hospitals Leuven, Belgium, said in a press release that the approval was “welcome news for patients with advanced or recurrent endometrial cancer in Europe, especially those with mismatch repair proficient disease, who have limited options.” The two regimens had the potential to improve outcomes for all patients, regardless of mismatch repair status,” she said.

AstraZeneca’s executive vice president, Dave Fredrickson, said that endometrial cancer is the fourth most common cancer in women in Europe and, until now, the majority with dMMR disease have had few available treatment options. He described the approval of the combined regimen as “a major step forward for patients.”