AstraZeneca mAb Approved by FDA for Endometrial Cancer Patients

Imfinzi, the brand name of AstraZeneca’s human monoclonal antibody (mAb), durvalumab, was approved by FDA in combination with the chemotherapy drugs carboplatin and paclitaxel, followed by Imfinzi monotherapy, for use in adult patients with mismatch repair deficient (dMMR) primary advanced or recurrent endometrial cancer. AstraZeneca announced the approval in a June 17, 2024 press release (1).

The approval follows the reporting of results of a DUO-E/GOG-3041/ENGOT-EN10 Phase III trial (ClinicalTrials.gov identifier NCT04269200), a randomized, double-blind, and placebo-controlled trial conducted in 22 countries, as published in the Journal of Clinical Oncology (2,3). In this trial of almost 700 patients, the risk of disease progression or death was decreased by 58% in dMMR endometrial cancer patients versus chemotherapy alone, according to AstraZeneca (1).

Endometrial cancer, which originates in the tissue lining of the uterus, is the sixth-most common cancer in women across the world, most commonly affecting women who have experienced menopause, with the average age at diagnosis being over 60 (1). Cases and deaths are expected to increase by 61% and 87%, from 420,400 and 97,700, respectively, in 2022 to 676,300 and 183,100 by 2050.

“With the incidence and mortality of endometrial cancer expected to continue to increase significantly in the coming decades, it is more important than ever that we bring new treatment options to patients at the earliest possible moment in their care,” Shannon N. Westin, professor of gynecologic oncology and reproductive medicine at The University of Texas MD Anderson Cancer Center and principal investigator of the trial, said in the AstraZeneca release. “This approval underlines clear evidence that durvalumab plus chemotherapy followed by durvalumab monotherapy delivers important clinical benefits for patients with mismatch repair deficient endometrial cancer.”

In endometrial cancer patients diagnosed at an early stage of the disease—where it is confined to the uterus—AstraZeneca said the five-year survival rate is between 80% and 90% (1). But at stages III and IV, that rate falls to below 20%, a sense of urgency not lost on Dave Fredrickson, AstraZeneca executive vice president, oncology business unit.

“There have been limited advances in the treatment of endometrial cancer in the last few decades, and continued innovation is critical as the burden of this cancer is expected to grow in the future,” he said. “Immunotherapy in combination with chemotherapy is emerging as a new standard of care in this setting, and the approval of Imfinzi offers an important new option for patients with mismatch repair deficient disease.”

FDA recommends a dose of durvalumab with carboplatin plus paclitaxel every three weeks for six cycles, followed by single-agent durvalumab every four weeks (4).

References

1. AstraZeneca. Imfinzi Plus Chemotherapy Approved in the US for Mismatch Repair Deficient Advanced or Recurrent Endometrial Cancer. Press Release. June 17, 2024. astrazeneca.com/media-centre/press-releases/2024/imfinzi-approved-in-the-us-for-endometrial-cancer.html
2. ClinicalTrials.gov. Study Details | Durvalumab With or Without Olaparib as Maintenance Therapy After First-Line Treatment of Advanced and Recurrent Endometrial Cancer (DUO-E). clinicaltrials.gov, March 5, 2024 (accessed June 20, 2024). clinicaltrials.gov/study/NCT04269200
3. Westin, S.N.; Moore, K.; Chon, H.S.; et al. Durvalumab Plus Carboplatin/Paclitaxel Followed by Maintenance Durvalumab With or Without Olaparib as First-Line Treatment for Advanced Endometrial Cancer: The Phase III DUO-E Trial. J. Clin. Oncol. 2023, 42 (3) 283–299. DOI: 10.1200/JCO.23.02132.
4. FDA. FDA Approves Durvalumab with Chemotherapy for Mismatch Repair Deficient Primary Advanced or Recurrent Endometrial Cancer. Press Release. June 14, 2024. fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-chemotherapy-mismatch-repair-deficient-primary-advanced-or-recurrent