Keytruda (pembrolizumab)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company:

Approval Status:

Approved July 2019

Specific Treatments:

recurrent esophageal cancer with PD-L1 expressing tumors

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General Information

Keytruda (pembrolizumab) is a programmed death receptor-1 (PD-1)-blocking antibody.

Keytruda is specifically indicated for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 [Combined Positive Score (CPS) ≥10] as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.

Keytruda is supplied as an injection for intravenous administration. The recommended dose of Keytruda for esophageal cancer is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.  

Clinical Results

FDA Approval

The FDA approval of Keytruda for esophageal cancer was based on the KEYNOTE-181 and KEYNOTE-180 clinical trials.  

KEYNOTE-181 was a multicenter, randomized, open-label, active-controlled trial that enrolled 628 patients with recurrent locally advanced or metastatic esophageal cancer whose tumors express PD-L1 and who progressed on or after one prior line of systemic treatment for advanced disease. Patients were randomized (1:1) to receive either Keytruda 200 mg every three weeks or investigator’s choice of any of the following chemotherapy regimens, all given intravenously: paclitaxel 80-100 mg/m2 on Days 1, 8, and 15 of every four-week cycle, docetaxel 75 mg/m2 every three weeks, or irinotecan 180 mg/m2 every two weeks. Treatment with Keytruda or chemotherapy continued until unacceptable toxicity or disease progression. The trial met its primary endpoint of significantly improving overall survival (OS), with a 31% decrease in the risk of death compared to a chemotherapy regimen of paclitaxel, docetaxel or irinotecan.

 KEYNOTE-180 was a multicenter, non-randomized, open-label trial that enrolled 121 patients with locally advanced or metastatic esophageal cancer who progressed on or after at least two prior systemic treatments for advanced disease. With the exception of the number of prior lines of treatment, the eligibility criteria were similar to and the dosage regimen identical to KEYNOTE-181. The major efficacy outcome measures were objective response rate (ORR) and duration of response (DoR). The ORR in the 35 patients with ESCC expressing PD-L1 (CPS ≥10) was 20%. Among the seven responding patients, the DoR ranged from 4.2 to 25.1+ months, with five patients (71%) having responses of six months or longer and three patients (57%) having responses of 12 months or longer.

Side Effects

Adverse effects associated with the use of Keytruda as a single agent may include, but are not limited to, the following:

fatigue

musculoskeletal pain

decreased appetite

pruritus

diarrhea

nausea

rash

pyrexia

cough

dyspnea

constipation

pain

abdominal pain

Mechanism of Action

Keytruda (pembrolizumab) is a programmed death receptor-1 (PD 1)-blocking, humanized monoclonal IgG4 kappa antibody. Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors. Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. 

Additional Information

For additional information regarding Keytruda or recurrent esophageal cancer with PD-L1 expressing tumors, please visit the Keytruda web site.