The FDA has granted accelerated approval to pembrolizumab for the treatment of any solid tumor in the body with a specific genetic feature, or biomarker. Until now, FDA approval for cancer treatments has been based on the location in the body where the tumor originated.
The FDA only utilizes the accelerated approval pathway when a drug is predicted to provide a clinical benefit in an area of unmet medical need and to significantly improve the safety or effectiveness of treating, diagnosing, or preventing a serious condition.
Pembrolizumab helps the body’s own immune system to fight cancer cells by targeting PD-1 and is now indicated for the treatment of adult and pediatric patients with unresectable or metastatic solid tumors that have been identified as having a biomarker referred to as microsatellite instability-high (MSI-H) or mismatch repair–deficient (dMMR), according to a statement issued by the FDA. A high mutational load in a tumor increases the probability of recognition by the immune system, and dMMR tumors carry more mutations than mismatch repair–proficient tumors.
Mismatch repair deficiency is a mechanism of DNA repair that occurs in a variety of tumor types. Tumors with these biomarkers are most commonly found in colorectal (up to 20% of sporadic colorectal cancers and all colorectal cancers associated with Lynch syndrome), endometrial, and gastrointestinal cancers, but they can also appear in the breast, prostate, bladder, thyroid gland, and other sites.
Approval for the new indication was based on the previously established benefit of pembrolizumab for the treatment of colorectal cancer. In a phase 2 study of colorectal cancer patients treated with the drug, the presence of mismatch repair–deficiency within the tumor robustly predicted benefit. Nearly two-thirds of patients whose tumors demonstrated mismatch repair–deficiency showed a response to pembrolizumab, whereas no patients with mismatch repair–proficient tumors responded to the drug.
To establish the safety and efficacy of pembrolizumab for this indication, patients with MSI-H or dMMR solid tumors were enrolled in 1 of 5 uncontrolled, single-arm clinical trials. A total of 15 cancer types were identified among 149 patients enrolled, with the most common types being colorectal, endometrial, and other gastrointestinal cancers. Of the 149 patients who received the study drug, 39.6% had a complete or partial shrinkage of their tumors, and in 78% of those patients, the response lasted for 6 months or more.
According to an FDA press release, the new indication covers those patients whose disease has progressed following prior treatment and who have no satisfactory alternative treatment options, as well as patients with colorectal cancer that has progressed following treatment with certain chemotherapy drugs. The FDA previously approved pembrolizumab for the treatment of metastatic melanoma, metastatic non–small cell lung cancer, recurrent or metastatic head and neck cancer, refractory classical Hodgkin lymphoma, and urothelial carcinoma.