Pembrolizumab Receives FDA Approval for Advanced Endometrial (Uterine) Cancer Treatment

For patients with high microsatellite instability (MSI-H) or DNA mismatch repair deficiency (dMMR) and advanced endometrial carcinoma (uterine cancer) whose cancer has progressed after prior systemic treatment in any setting and who are not candidates for curative surgery or radiotherapy, pembrolizumab (Keytruda, Merck) received FDA (US Food and Drug Administration) approval as a single agent on March 21, 2022.

The FDA simultaneously approved the VENTANA MMR RxDx Panel (Ventana Medical Systems/Roche Tissue Diagnostics) as a companion diagnostic device to select patients with dMMR solid (organ) tumors eligible for pembrolizumab treatment. The FDA had previously approved FoundationOne CDx (F1CDx, Foundation Medicine, Inc.) as a companion diagnostic device to select patients with MSI-H solid tumors eligible for pembrolizumab.

FDA Approval Based on the KEYNOTE-158 Study

Results from Cohorts D and K of KEYNOTE-158 led to FDA approval of pembrolizumab for this indication. These cohorts enrolled 90 patients with unresectable or metastatic MSI-H or dMMR endometrial carcinoma. Tumor MSI-H and dMMR status were determined, respectively, using polymerase chain reaction (PCR) or immunohistochemistry. Patients received 200 mg pembrolizumab every 3 weeks until unacceptable toxicity or documented disease progression. Patients treated with pembrolizumab who had no disease progression received treatment for up to 24 months.

The main efficacy outcome measures, assessed by blinded independent central review according to RECIST v1.1, were objective response rate (ORR) and duration of response (DoR).

Results

• The objective response rate was 46% (95% CI: 35, 56).
• Median duration of response was not reached among responders (2.9 to 55.7+).
• Among responders, 68% had a response duration ≥12 months and 44% had a response duration ≥24 months.

The most common adverse reactions in patients (≥20%) were fatigue, musculoskeletal pain, rash, diarrhea, fever, cough, decreased appetite, itching, shortness of breath, constipation, pain, abdominal pain, nausea, and hypothyroidism. Immune-mediated adverse effects are also associated with pembrolizumab; these include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin adverse reactions.

The recommended pembrolizumab dose is 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months.