FDA Approves Durvalumab Plus Chemotherapy to Treat Endometrial Cancer

The FDA has approved durvalumab (Imfinzi; AstraZeneca) in combination with carboplatin and paclitaxel, followed by durvalumab monotherapy to treat individuals with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR).¹

Female reproductive system diseases.uterus cancer and endometrial malignant tumor as a uterine medical concept.3d illustration - Image credit: Crystal light | stock.adobe.com

Endometrial cancer is marked as the sixth most common cancer among women worldwide, as it commonly occurs in women that have undergone menopause, with the average diagnosis age of 60 years and older. The study authors noted that the disease derives in the tissue lining of the uterus and is highly heterogeneous. Most cases of endometrial cancer are found at an early stage that is typically treated with surgery and/or radiation, resulting in 5-year survival at 80% to 90%. However, if diagnosed in an advanced stage, the 5-year survival rate decreases to less than 20%.¹

“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 [durvalumab] offers an important new option for patients with mismatch repair deficient disease,” said Dave Fredrickson, executive vice president, Oncology Business Unit, AstraZeneca, in a news release.¹

In 2022, among 66,000 diagnosed individuals, there were nearly 12,000 deaths. However, the study authors noted that an increase of incidence and mortality of endometrial cancer is reported to occur in 2050, from 61% to 87% respectively. This includes the 20% to 30% of individuals with dMMR disease, highlighting the need for more treatment options.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 investigator of the trial Shannon N. Westin, professor of gynecologic oncology and reproductive medicine at The University of Texas MD Anderson Cancer Center, in a news release.¹

According to the study authors, as a human monoclonal antibody, durvalumab binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, offsetting the tumor’s immune attack, altering immune responses.¹ In addition to this approval, durvalumab was previously approved to treat non-small cell lung cancer, extensive-stage small cell lung cancer, bile duct cancer, gallbladder cancer, and unresectable hepatocellular carcinoma.²

The current approval was granted based on positive results from the 3-arm, randomized, double-blind, placebo-controlled, multicenter, phase 3 DUO-E trial (NCT04269200). The study assessed durvalumab as first- line treatment with platinum-based chemotherapy (carboplatin and paclitaxel), followed by durvalumab monotherapy or durvalumab with olaparib (Lynparza; AstraZeneca and Merck & Co) as maintenance therapy compared to platinum-based chemotherapy alone.¹

The trial included 699 individuals that were newly diagnosed with advanced or recurrent epithelial endometrial carcinoma that were randomly assigned to receive 1120 mg of durvalumab or placebo, followed by chemotherapy. Following 4 to 6 cycles of chemotherapy, the individuals then received 15,000 mg of durvalumab or placebo as maintenance, in addition to 300 mg of olaparib or a placebo.¹

The results displayed that durvalumab plus carboplatin and paclitaxel, continued with durvalumab monotherapy, decreased the risk of disease progression or death by 58% among individuals with dMMR endometrial cancer, compared to just chemotherapy, according to study authors.¹

“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,” said Westin, in a news release.¹

References

1. Imfinzi plus chemotherapy approved in the US for mismatch repair deficient advanced or recurrent endometrial cancer. AstraZeneca. News release. 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. IMFINZI. IMFINZI is an immunotherapy that is approved to treat certain cancers. January 2024. Accessed June 17, 2024. https://www.imfinzi.com/?source=imz_n_c_709&umedium=cpc&uadpub=google&ucampaign=cndtcbbrmltpimfazcorebrandalone&ucreative=brandedalonetxtnationalaa1ph&uplace=imfinziastrazeneca&outcome=dtc&cmpid=1&gclid=Cj0KCQjwvb-zBhCmARIsAAfUI2vsZ7hcEweCxwGDtOixoHiAByU_Gf0MBjgbQGR23CXBP22gRjbkSQEaAthPEALw_wcB&gclsrc=aw.ds