The US Food and Drug Administration (FDA) has granted full approval to Keytruda (pembrolizumab) for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumors, as determined by an FDA-approved test, whose disease has progressed after prior treatment and who have no satisfactory alternative treatment options. 

Keytruda was previously granted accelerated approval for this indication. The conversion to regular approval was based on data from 3 phase 2 trials — KEYNOTE-158 ( Identifier: NCT02628067), KEYNOTE-164 ( Identifier: NCT02628067), and KEYNOTE-051 ( Identifier: NCT02628067) — which included 504 patients with more than 30 types of cancer.

KEYNOTE-158 enrolled 373 patients with advanced MSI-H/dMMR non-colorectal cancers who had disease progression following prior therapy. KEYNOTE-164 included 124 patients with advanced MSI-H/dMMR colorectal cancer that progressed following treatment with fluoropyrimidine and either oxaliplatin or irinotecan with or without anti-VEGF/EGFR monoclonal antibody-based therapy. KEYNOTE-051 included 7 pediatric patients with MSI-H/dMMR cancers.

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Adult patients received pembrolizumab at 200 mg intravenously every 3 weeks, and pediatric patients received 2 mg/kg every 3 weeks until acceptable toxicity, disease progression, or a maximum of 24 months. The main efficacy outcome measures were overall response rate (ORR) and duration of response (DOR).

In a pooled analysis of the trials, the ORR was 33.3% at a median follow-up of 20.1 months. The complete response rate was 10.3%, and the partial response rate was 23.0%.

Among the 168 responders, 77% had responses lasting 12 months or longer, and 39% had responses lasting 36 months or longer. The median DOR was 63.2 months.

Among patients with MSI-H/dMMR colorectal cancer (n=124), the ORR was 34%, and the DOR ranged from 4.4 to 58.5+ months. Among patients with other MSI-H/dMMR non-colorectal solid tumors (n=380), the ORR was 33%, and the DOR ranged from 1.9+ to 63.9+ months.

Non-colorectal solid tumors included endometrial cancer, gastric or gastroesophageal junction cancer, small intestinal cancer, brain cancer, ovarian cancer, biliary cancer, pancreatic cancer, sarcoma, breast cancer, cervical cancer, neuroendocrine cancer, prostate cancer, adrenocortical cancer, mesothelioma, thyroid cancer, small cell lung cancer, bladder cancer, salivary cancer, renal cell cancer, and other cancers.


FDA converts to full approval indication for Keytruda® (pembrolizumab) for certain adult and pediatric patients with advanced microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors. News release. Merck. Accessed March 30, 2023.

This article originally appeared on MPR