FDA approves Imfinzi regimen for advanced endometrial cancer
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The FDA approved the use of durvalumab in combination with carboplatin and paclitaxel followed by single-agent durvalumab for women with mismatch repair-deficient primary advanced or recurrent endometrial cancer.
Durvalumab (Imfinzi, AstraZeneca) —a human monoclonal antibody that binds to PD-L1 — is approved for use in several countries, including indications for unresectable stage III non-small cell lung cancer, in combination with tremelimumab (Imjudo, AstraZeneca) and chemotherapy for metastatic non-small cell lung cancer, in combination with chemotherapy in locally advanced or metastatic biliary tract cancer and in combination with tremelimumab in unresectable hepatocellular carcinoma.
FDA based approval on results from the double-blind, placebo-controlled DUO-E trial, which assessed efficacy of the regimen in 699 women with primary advanced or recurrent endometrial cancer.
Researchers randomly assigned patients in a 1:1:1 ratio to one of three treatment arms, with study participants receiving either 1,120 mg durvalumab or placebo with carboplatin and paclitaxel every 3 weeks for a maximum of six cycles, followed by 1,500 mg durvalumab or placebo every 4 weeks as maintenance therapy until disease progression, or an additional investigational combination regimen.
PFS served as the study’s major efficacy outcome measurement.
The durvalumab-based regimen conferred statistically significant improvement in PFS among the overall study population compared with placebo; however, the strongest improvement occurred among patients with mismatch repair-deficient tumors, according to an FDA press release.
Median PFS had not been reached among 95 patients with mismatch repair-deficient tumors in the durvalumab arm compared with median PFS of 7 months (95% CI, 6.7–14.8) in the placebo arm (HR = 0.42; 95% CI, 0.22–0.8).
“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, MD, MPH, FACOG, professor of gynecologic oncology and reproductive medicine at The University of Texas MD Anderson Cancer Center and principal investigator of the trial, said in an AstraZeneca 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.”
Adverse reactions occurring in at least 25% of patients treated with durvalumab in combination with carboplatin and paclitaxel included peripheral neuropathy, musculoskeletal pain, nausea, alopecia, fatigue, abdominal pain, constipation, rash, diarrhea, vomiting, and cough.
The recommended durvalumab dose for patients with a body weight of at least 30 kg is 1,120 mg with carboplatin plus paclitaxel every 3 weeks for six cycles, followed by single-agent durvalumab 1,500 mg every 4 weeks, with a recommended durvalumab dose for patients with a body weight less than 30 kg of 15 mg/kg with carboplatin and paclitaxel every 3 weeks for six cycles, followed by durvalumab 20 mg/kg every 4 weeks.
References:
- FDA approves durvalumab with chemotherapy for mismatch repair deficient primary advanced or recurrent endometrial cancer (press release). Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-chemotherapy-mismatch-repair-deficient-primary-advanced-or-recurrent. Published June 14, 2024. Accessed June 18, 2024.
- Imfinzi plus chemotherapy approved in the US for mismatch repair deficient advanced or recurrent endometrial cancer (press release). Available at: https://www.astrazeneca.com/media-centre/press-releases/2024/imfinzi-approved-in-the-us-for-endometrial-cancer.html. Published June 17, 2024. Accessed June 18, 2024.
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