FDA Approves Imfinzi (Durvalumab) in Combination with Chemotherapy for Adults with Mismatch Repair-Deficient (dMMR) Primary Advanced or Recurrent Endometrial Cancer

Jul 08, 2024 15:30 CST Updated Jul 07, 17:30

AstraZeneca

Biopharmaceutical Manufacturer

On June 14, 2024, the U.S. FDA approvedAstraZenecaThe heavy-duty PD-L1 inhibitorImfinzi (durvalumab, durvalumab)In combination with carboplatin and paclitaxel, followed by Imfinzi monotherapy maintenance, for the treatment of primary advanced or recurrent mismatch repair deficient (dMMR)Adult patients with endometrial cancer。

Imfinzi Key Studies

This approval is based onDUO-E Phase IIIResults of the pre-specified exploratory subgroup analysis based on MMR status in the trial. The results of DUO-E have been published in the Journal of Clinical Oncology.

Original link:

Shannon N. Westin 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. JCO 42, 283-299(2024).

DUO-E Trial(GOG 3041/ENGOT-EN10) is a three-arm, randomized, double-blind, placebo-controlled, multicenter Phase III trial, using first-line Imfinzi plus platinum-based chemotherapy (carboplatin and paclitaxel) as the foundation treatment, followed by either Imfinzi monotherapy or Imfinzi combined with olaparib as maintenance therapy, compared to platinum-based chemotherapy alone, for newly diagnosed advanced or recurrent endometrial cancer patients.

DUO-E Trial Included699 casesNewly diagnosed patients with advanced or recurrent endometrial cancer were randomized to receive Imfinzi (1120mg) or placebo every three weeks, in combination with standard platinum-based chemotherapy. After 4-6 cycles of chemotherapy, patients (without disease progression) received maintenance treatment with Imfinzi (1500mg) or placebo every four weeks, plus olaparib (300mg BID [2x150mg tablets, twice daily]) or placebo treatment until disease progression.

In the trial, compared with chemotherapy, Imfinzi plus carboplatin and paclitaxel followed by Imfinzi maintenance monotherapyCan reduce the risk of disease progression or death by 58% in patients with dMMR endometrial cancer.(Hazard ratio 0.42; 95% confidence interval 0.22-0.80).

The most common adverse reactions (>25%) of Imfinzi in combination with carboplatin and paclitaxel are peripheral neuropathy, musculoskeletal pain, nausea, alopecia, fatigue, abdominal pain, constipation, rash, diarrhea, vomiting, and cough.

Imfinzi (Durvalumab)

Imfinzi (durvalumab, durvalumab)It is a humanized PD-L1 monoclonal antibody that blocks the binding of PD-L1 to PD-1 and CD80, thereby interrupting tumor immune escape strategies and restoring suppressed immune responses.

Since its first approval in May 2017, Imfinzi has been exploring its use as a monotherapy or in combination with other anti-cancer drugs.Treatment of small cell lung cancer, non-small cell lung cancer, bladder cancer, breast cancer, various gastrointestinal tumors, and other solid tumors.

Endometrial Cancer

Endometrial CancerIt is a highly heterogeneous disease that originates from endometrial tissue, most commonly found in postmenopausal women, with an average age of diagnosis over 60 years.

In the United States,Endometrial cancer is the fourth most common cancer in women.In 2022, more than 66,000 patients were diagnosed, and nearly 12,000 died. For patients diagnosed early,The five-year survival rate is approximately 80-90%., but for patients with advanced stages, new treatment options are urgently needed as their survival rate is less than 20%.

The University of Texas MD Anderson Cancer CenterProfessor of Gynecologic Oncology and Reproductive Medicine and the trial's principal investigator Shannon N. Westin stated, "The incidence and mortality of endometrial cancer are expected to continue rising significantly in the coming decades. Therefore, there is a greater need than ever before to provide new treatment options to patients early in their treatment journey. This approval clearly demonstrates that the combination of durvalumab with chemotherapy, followed by maintenance therapy with durvalumab alone, offers significant clinical benefits for patients with mismatch repair-deficient endometrial cancer."

Reference Source:

[1]https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-chemotherapy-mismatch-repair-deficient-primary-advanced-or-recurrent

[2]https://www.astrazeneca.com/media-centre/press-releases/2024/imfinzi-approved-in-the-us-for-endometrial-cancer.html

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