The following is a message from the Director of the FDA Oncology Center of Excellence, Dr. Richard Pazdur
On March 21, 2022, the Food and Drug Administration approved pembrolizumab (Keytruda, Merck), as a single agent, for patients with advanced endometrial carcinoma that is microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and who are not candidates for curative surgery or radiation.
Today, the FDA also approved the VENTANA MMR RxDx Panel (Ventana Medical Systems / Roche Tissue Diagnostics) as a companion diagnostic device to select patients with dMMR in solid tumors that are eligible for treatment with pembrolizumab. The FDA previously approved the FoundationOne CDx (F1CDx, Foundation Medicine, Inc.) as a companion diagnostic device to select patients with MSI-H in solid tumors that are eligible for treatment with pembrolizumab.
Efficacy was evaluated in KEYNOTE-158 (NCT02628067), a multicenter, non-randomized, open-label, multi-cohort trial in 90 patients with unresectable or metastatic MSI-H or dMMR endometrial carcinoma in Cohorts D and K. MSI or MMR tumor status was determined using polymerase chain reaction or immunohistochemistry, respectively. Patients received pembrolizumab 200 mg intravenously every 3 weeks until unacceptable toxicity or documented disease progression. Patients treated with pembrolizumab without disease progression could be treated for up to 24 months.
The major efficacy outcome measures were objective response rate (ORR) and duration of response (DoR) as assessed by blinded independent central review according to RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. ORR was 46% (95% CI: 35, 56). Median DoR was not reached (2.9, 55.7+), with 68% having response durations ≥12 months and 44% having response durations ≥24 months.
The most common adverse reactions (≥20%) occurring in patients were fatigue, musculoskeletal pain, rash, diarrhea, pyrexia, cough, decreased appetite, pruritis, dyspnea, constipation, pain, abdominal pain, nausea, and hypothyroidism. Immune-mediated side 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.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
- FDA: Coronavirus Disease 2019 (COVID-19)
- NCI: Coronavirus: What People With Cancer Should Know
- CDC: Coronavirus (COVID-19)
Please visit the FDA Hematology/Oncology (Cancer) Approvals & Safety Notifications webpage for a list of current and past approvals.