On March 21, 2022, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda®) as a single agent for patients with microsatellite instability–high (MSI-H) or mismatch repair deficient (dMMR) advanced endometrial carcinoma, 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.
FDA also approved the VENTANA MMR RxDx Panel as a companion diagnostic device to select patients with dMMR in solid tumors that are eligible for treatment with pembrolizumab. FDA previously approved the FoundationOne CDx 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 a multicenter, nonrandomized, open-label, multicohort trial (KEYNOTE-158; NCT02628067) involving 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 via IV every three weeks for up to 24 months or until they experienced unacceptable toxicity or disease progression.
The major efficacy outcome measures were objective response rate (ORR) and duration of response (DoR) as assessed by blinded independent central review according to response evaluation criteria in solid tumors 1.1, 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 of at least 12 months and 44% having response durations of at least 24 months.
The most common adverse reactions reported by 20% or more of patients were fatigue, musculoskeletal pain, rash, diarrhea, pyrexia, cough, decreased appetite, pruritis, dyspnea, constipation, pain, abdominal pain, nausea, and hypothyroidism. Immune-mediated side effects included pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin adverse reactions.
The recommended pembrolizumab dose is 200 mg every three weeks or 400 mg every six weeks until patients experience disease progression, unacceptable toxicity, or up to 24 months.
View the full prescribing information for pembrolizumab.
The review used the Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment.
Healthcare professionals should report all serious adverse events they suspect are associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.
For assistance with single-patient investigational new drug applications for oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.