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Recent FDA Approvals in Endometrial Cancer


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In recent months, the U.S. Food and Drug Administration approved two treatment options for patients with endometrial cancer, which are summarized herein.

Dostarlimab-gxly for dMMR Endometrial Cancer

On April 22, 2021, the FDA granted accelerated approval to dostarlimab-gxly (Jemperli) for adult patients with mismatch repair–deficient (dMMR) recurrent or advanced endometrial cancer, as determined by an FDA-approved test, that has progressed on or following a prior platinum-containing regimen.

Efficacy was evaluated based on cohort A1 in the GARNET trial (ClinicalTrials.gov identifier NCT02715284), a multicenter, multicohort, open-label trial in patients with advanced solid tumors. The efficacy population consisted of 71 patients with dMMR recurrent or advanced endometrial cancer whose disease progressed on or after a platinum-containing regimen. Patients received dostarlimab-gxly at 500 mg intravenously every 3 weeks for four doses followed by 1,000 mg intravenously every 6 weeks. The main efficacy endpoints were overall response rate and duration of response.

The confirmed overall response was 42.3% (95% confidence interval = 30.6%–54.6%); the complete response rate was 12.7% and partial response rate was 29.6%. Median duration of response was not reached, with 93.3% of patients having durations ≥ 6 months (range = 2.6–22.4 months, ongoing at last assessment).

Serious adverse reactions occurred in 34% of patients receiving dostarlimab-gxly. Serious adverse reactions in > 2% of patients included sepsis, acute kidney injury, urinary tract infection, abdominal pain, and pyrexia. The most common adverse reactions (≥ 20%) were fatigue/asthenia, nausea, diarrhea, anemia, and constipation. The most common grade 3 or 4 adverse reactions (≥ 2%) were anemia and increased transaminases. Immune-mediated adverse reactions can occur with the agent, including pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis.

Pembrolizumab Plus Lenvatinib for Advanced Endometrial Carcinoma

On July 21, 2021, the FDA granted regular approval to pembrolizumab (Keytruda) in combination with lenvatinib (Lenvima) for patients with advanced endometrial carcinoma that is not microsatellite instability–high (MSI-H) or dMMR. These patients must have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation therapy. The combination received accelerated approval for advanced endometrial carcinoma on September 17, 2019.

KEYNOTE-775/Study 309 (ClinicalTrials.gov identifier NCT03517449) was a multicenter, open-label, randomized, active-controlled trial required to confirm the clinical benefit of this accelerated approval (see full report on page 50). The study enrolled 827 patients with advanced endometrial carcinoma previously treated with at least one prior platinum-based chemotherapy regimen in any setting, including neoadjuvant and adjuvant treatments. Patients were randomly assigned 1:1 to receive either pembrolizumab at 200 mg intravenously every 3 weeks with lenvatinib at 20 mg orally once daily or investigator’s choice of doxorubicin or paclitaxel.

The major efficacy outcome measures were progression-free survival and overall survival.

For patients with advanced endometrial cancer that is not MSI-H or dMMR, the median progression-free survival was 6.6 months (95% CI = 5.6–7.4 months) for patients given pembrolizumab/lenvatinib and 3.8 months (95% CI = 3.6–5.0 months) for those given investigator’s choice chemotherapy (hazard ratio [HR] = 0.60, 95% CI = 0.50–0.72, P < .0001). Median overall survival was 17.4 months (95% CI = 14.2–19.9 months) and 12.0 months (95% CI = 10.8–13.3 months), respectively (HR = 0.68, 95% CI = 0.56–0.84, P = .0001).

The most common adverse reactions reported in ≥ 20% of patients in trials of pembrolizumab in combination with lenvatinib were hypothyroidism, hypertension, fatigue, diarrhea, musculoskeletal disorders, nausea, decreased appetite, vomiting, stomatitis, weight loss, abdominal pain, urinary tract infection, proteinuria, constipation, headache, hemorrhagic events, palmar-plantar erythrodysesthesia, dysphonia, and rash. 


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