New Indication for Cancer Drug Based on Biomarkers

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Pembrolizumab (Keytruda) has been approved for the treatment of unresectable or metastatic solid tumors that have either the microsatellite instability–high (MSI-H) or mismatch repair deficient (dMMR) genetic biomarker. This is the first time the Food and Drug Administration (FDA) has approved a cancer treatment based on a tumor's biomarker rather than the location in the body where the cancer originated.
Tumors with MSI-H and dMMR biomarkers have abnormalities that prevent normal cell repair by the immune system. Pembrolizumab is a humanized monoclonal antibody that blocks the PD-1/PD-L1 cellular pathway (PD-1 and its ligand, PD-L1, are proteins found on immune T-cell receptors). Stimulation of these receptors inhibits T-cell proliferation and cytokine production. Pembrolizumab's blocking of the PD-1/PD-L1 pathway allows for the release of an antitumor immune response, which plays a role in killing cancer cells. Pembrolizumab was previously approved to treat metastatic melanoma, metastatic non–small cell lung cancer, recurrent or metastatic head and neck cancer, refractory classical Hodgkin lymphoma, and urothelial cancer.
Pembrolizumab is indicated to treat either pediatric or adult patients with solid tumors that have progressed despite prior treatment and where no other treatment options exist. It can also be used to treat patients who have colorectal cancer that has progressed after treatment with certain chemotherapy drugs. Tumors with MSI-H or dMMR biomarkers are most commonly found in colorectal, endometrial, and gastrointestinal cancers but may also occur in cancers of the breast, prostate, bladder, and thyroid gland, among others. The biomarker must be detected by an FDA-approved test.
The FDA granted approval of pembrolizumab for this new indication using the accelerated approval pathway, meaning that although full clinical trials have not been conducted, it is believed based on findings of drug action that the drug will be helpful in treating a condition. In this case, the approval was granted based on the tumor response rate and how long the response was noted. In five uncontrolled, single-arm clinical trials, which enrolled 149 patients, 39.6% of patients had a complete or partial response to pembrolizumab. Of these, 78% had a response that lasted six months or longer. The drug's efficacy must now be proven through additional clinical trials, which the manufacturer is currently conducting, or the FDA approval will be withdrawn.
Pembrolizumab may induce immune-mediated adverse effects such as pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis. Infusion-related reactions can be severe and potentially life threatening. The most common adverse reactions (occurring in 20% or more of patients) include fatigue, pruritus, diarrhea, decreased appetite, rash, pyrexia, cough, dyspnea, musculoskeletal pain, constipation, and nausea.
Nurses should teach patients receiving pembrolizumab the signs and symptoms of the various immune-mediated responses and infusion-related reactions and instruct them to report these immediately to their health care team. Nurses should also educate patients on the common adverse effects of pembrolizumab, as well as assess patients for these effects.
To read the FDA News Release regarding pembrolizumab, go to For complete prescribing information, see
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