FDA Approves Pembrolizumab for Solid Tumors with MSI-H or dMMR Mutations for Select Patients

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On March 29, 2023, the U.S. Food and Drug Administration approved pembrolizumab for adult and pediatric patients with unresectable or metastatic solid cancers with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) mutations as detected by utilizing local or central polymerase chain reaction and local or central immunohistochemistry respectively. This approval builds on the accelerated approval of pembrolizumab in 2017 as the first tissue-agnostic therapy.


Study ID numbers: NCT02628067; NCT02460198; NCT02332668


The approval was based on multicenter, non-randomized, open-label, multicohort, phase II trials (KEYNOTE-158, KEYNOTE-164, and KEYNOTE-051) that included 504 adult and pediatric patients with over 30 kinds of unresectable or metastatic cancers that harbored MSI-H or dMMR mutations. These cancers had exhausted other treatment options or had no satisfactory alternative therapy. The dose of immunotherapy with pembrolizumab was 200 mg every three weeks for adults and 2 mg/kg every three weeks for pediatric patients. It was given until unacceptable toxicity, progressive disease, or for a maximum of 24 months.


Efficacy was established on objective response rate (ORR) and duration of response (DOR).


A pooled analysis was carried out from all the phase II trials mentioned above, and pembrolizumab was noted to show an ORR of 33.3% (95% CI, 29.2-37.6), including a complete response rate of 10.3% and partial response rate of 23%. 77% of all the patients who responded showed a lasting response for at least 12 months, and for 39% of patients, the response lasted for 36 months or longer. The duration of response was 63.2 months in the final analysis. The ORR for colorectal cancer (n=124) was demonstrated at 34% (95% CI, 26%-43%) with a DOR ranging from 4.4 to 58.5 months. Likewise, the ORR for non-colorectal solid tumors (n=380) was noted to be 33% (95% CI: 28%-38%) with a duration of response ranging from 1.9 to 63.9 months.


The expected adverse effects are the immune-mediated adverse effects that can occur during or after the treatment. Effects include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, and organ rejections, among others.

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