FDA Approves AstraZeneca’s Imfinzi for Mismatch Repair Deficient Primary Advanced or Recurrent Endometrial Cancer

Image Credit: Adobe Stock Images/Wayu

The FDA has approved AstraZeneca’s Imfinzi (durvalumab) in combination with chemotherapy, followed by Imfinzi monotherapy, for the treatment of adults with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR). According to the company, the approval is based on promising results from the DUO-E Phase III trial, which found that the Imfinzi combination therapy reduced the risk of disease progression or death by 58% in patients with dMMR endometrial cancer compared to chemotherapy alone.¹

“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,” said principal trial investigator Shannon N. Westin, professor of gynecologic oncology and reproductive medicine, The University of Texas MD Anderson Cancer Center, in a press 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.”

The three-arm, randomized, double-blind, placebo-controlled, multicenter DUO-E trial evaluated first-line Imfinzi (1120 mg) plus platinum-based chemotherapy (carboplatin and paclitaxel) followed by either Imfinzi monotherapy or Imfinzi plus Lynparza (olaparib) as maintenance therapy versus platinum-based solo chemotherapy for patients with either newly diagnosed advanced or recurrent endometrial cancer. Consisting of 699 patients, treatment was given every three weeks in addition to chemotherapy. At cycles 4-6, patients who did not experience disease progression received either a 1500 mg treatment of Imfinzi or placebo every four weeks as maintenance, plus 300 mg Lynparza (300 mg BID [2x150mg tablets, twice a day]) or placebo until disease progression. The primary endpoint of the study was progression-free survival, with secondary endpoints including overall survival, safety, and tolerability.

The results, published in the Journal of Clinical Oncology, found that durvalumab had a 29% lower risk of disease progression or death versus control. Additionally, the combination therapy was found to have a 45% lower risk of disease progression or death versus control.^1,2

AstraZeneca stated that the safety and tolerability profile of the combination was consistent with previous findings, with no new safety signals reported. Adverse events (AEs) included anemia, nausea, fatigue or asthenia, and alopecia through the duration of the study. During the maintenance phase of the study, the only AEs reported were nausea, anemia, and fatigue or asthenia. In most cases, AEs were handled through dose modification instead of treatment discontinuation. In the control arm of the study, 18.6% ended treatment, with 20.9% in the durvalumab arm, and 24.4% in the durvalumab plus olaparib arm, respectively.¹

In the United States, endometrial cancer is the most common form of cancer. It is expected that by the end of 2024, 13,250 women will die from the disease. Additionally, it is considered to be one of the few cancers with an increasing mortality rate, with the death rate rising around 1.7% per year since the early 2000s.³

“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. 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,” said Dave Fredrickson, EVP, oncology business unit, AstraZeneca, in the press release.

References

1. Imfinzi plus chemotherapy approved in the US for mismatch repair deficient advanced or recurrent endometrial cancer. AstraZeneca. June 17, 2024. Accessed June 17, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/imfinzi-approved-in-the-us-for-endometrial-cancer.html#!

2. 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. ASCO. October 21, 2023. Accessed June 17, 2024. https://ascopubs.org/doi/full/10.1200/JCO.23.02132

3. Key Statistics for Endometrial Cancer. American Cancer Society. Accessed June 17, 2024. https://www.cancer.org/cancer/types/endometrial-cancer/about/key-statistics.html