On March 21, 2022, pembrolizumab was approved for patients with advanced endometrial carcinoma that is microsatellite instability–high (MSI-H) or mismatch repair–deficient (dMMR), as determined by a U.S. Food and Drug Administration (FDA)-approved test, who have disease progression following prior systemic therapy in any setting, and who are not candidates for curative surgery or radiation.1
The FDA simultaneously approved the VENTANA MMR RxDx Panel as a companion diagnostic device to select patients with dMMR in solid tumors who are eligible for pembrolizumab treatment. The FoundationOne CDx was previously approved as a companion diagnostic device to select patients with MSI-H in solid tumors who are eligible for pembrolizumab treatment.
Supporting Efficacy Data
Approval was based on findings in two cohorts (D and K) of the KEYNOTE-158 study (ClinicalTrials.gov identifier NCT02628067). In these cohorts, 90 patients with unresectable or metastatic MSI-H or dMMR endometrial carcinoma received pembrolizumab at 200 mg every 3 weeks until disease progression, unacceptable toxicity, or for up to 24 months.
Pembrolizumab has warnings/precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryofetal toxicity.
Response was assessed on blinded independent central review according to Response Evaluation Criteria in Solid Tumors version 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. An objective response was observed in 41 patients (46%, 95% confidence interval [CI] = 35%–56%), with a complete response in 12%. Median duration of response was not reached (range = 2.9–55.7+ months), with 68% of responses lasting at least 12 months and 44% lasting at least 24 months
How It Is Used
The recommended dose of pembrolizumab is 200 mg every 3 weeks or 400 mg every 6 weeks until disease progression, unacceptable toxicity, or up to 24 months.
No dose reductions of pembrolizumab are recommended. In general, pembrolizumab should be withheld for grade 3 immune-mediated adverse reactions and permanently discontinued for grade 4 immune-mediated adverse reactions, recurrent grade 3 immune-mediated reactions requiring systemic immunosuppressive treatment, or an inability to reduce corticosteroid dose to up to 10 mg prednisone or equivalent per day within 12 weeks of initiating steroids. Prescribing information provides instructions on dosage modifications for immune-mediated adverse reactions and infusion-related reactions.
The most common adverse events of any grade (≥ 20%) in patients receiving single-agent pembrolizumab in clinical trials have been fatigue, musculoskeletal pain, rash, diarrhea, pyrexia, cough, decreased appetite, pruritus, dyspnea, constipation, pain, abdominal pain, nausea, and hypothyroidism. Prescribing information does not provide adverse event data for the 90 patients treated with pembrolizumab for endometrial cancer in the KEYNOTE-158 cohorts; it notes that adverse events were similar to those occurring in 2,799 patients with melanoma or non–small cell lung cancer treated with pembrolizumab as a single agent.
Pembrolizumab has warnings/precautions for immune-mediated adverse reactions, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, dermatologic reactions, and solid organ transplant rejection; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation; and embryofetal toxicity. Patients should be advised not to breastfeed while receiving pembrolizumab.
1. Keytruda (pembrolizumab) injection for intravenous use prescribing information, Merck & Co, March 2022. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/125514s110lbl.pdf. Accessed on March 30, 2022.