Keytruda is an immunotherapy drug that uses a patient’s own immune system to attack and kill cancer cells. The therapy is currently in clinical trials to test its efficacy as a mesothelioma cancer treatment.
Keytruda, also known by its generic name pembrolizumab, has been approved to treat non-small cell lung cancer (NSCLC), melanoma and head and neck squamous cell cancer (HNSCC), among other cancers. The drug has not received U.S. Food and Drug Administration approval for treatment of malignant mesothelioma cancer, but has shown promise in extending life expectancy with minimal side effects through clinical trials. Without FDA approval, Keytruda is considered an experimental treatment and is only available to mesothelioma patients through clinical trials.
How Keytruda Treats Mesothelioma
Keytruda is an immunotherapy drug categorized as an immune checkpoint inhibitor, a type of monoclonal antibody. The drug works by blocking the PD-L1 protein, which is a protein that can be found on normal and cancer cells. The protein is used by cancer cells to trick a patient's T-cells (a type of white blood cell that detects and fights disease) into thinking the cancer is a healthy, functioning cell. Without Keytruda, or another anti-PD-1 drug, the cancer cell uses the PD-L1 protein to connect with the PD-1 protein on the T-cell. This connection prevents the T-cell from attacking and allows the cancer to grow and spread. Keytruda blocks the PD-L1 receptor on mesothelioma cancer cells, making them vulnerable to attack from the body’s immune system.
Keytruda is administered via IV (intravenous therapy) for 30-minute increments every three weeks. Typically, courses of treatment continue until the patient can no longer endure the toxicity of the medication. Because the treatment is still in clinical trials, Keytruda is often used as a second-line treatment for mesothelioma patients whose disease did not respond or recurred after first-line treatment with either surgery, radiation or chemotherapy. Using the medication as a second-line treatment has shown promising results in preliminary clinical trials.
A clinical trial, KEYNOTE-028, conducted in 13 different sites across six different countries has found success using Keytruda to treat malignant pleural mesothelioma patients who were previously treated with chemotherapy or were considered ineligible for treatment. Researchers reported that 14 of 25 participants (56%) experienced a reduction in tumor size. Additionally, the average overall survival with Keytruda was 18 months, and patients in the trial averaged six months with no disease progression. The average overall survival rate reported in the trial is a promising result of treatment, as the typical life expectancy for pleural mesothelioma patients is six months to one year. Researchers further noted that for patients who receive a second-line treatment, prognosis is typically six to seven months.
The efficacy of the treatment option is still being tested, with various ongoing clinical trials. Currently, a phase II trial is working to continue the success achieved thus far in KEYNOTE-028. The trial, conducted at The University of Chicago Medicine Comprehensive Cancer Center, has found patients treated with Keytruda experienced a 21% response rate and a 76% disease control rate so far. Though overall median survival will not be concluded until the trial’s end, researchers noted a median progression-free survival of 6.2 months.
Both trials are still underway and results will continue to be reported. The studies are anticipated to be completed within the next few years, and will hopefully lead to further research to achieve FDA approval for the drug.
Eligibility for Keytruda
Eligibility for pleural mesothelioma treatment with Keytruda varies, as the drug is only available through participation in clinical trials. Clinical trials may accept patients based on their own self-determined criteria. The requirements for participation may be as broad as being diagnosed with a specific cancer, like pleural mesothelioma. However, some trials may specify the stage, cell type or prior treatment methods of desired patients. Patients interested in joining a Keytruda clinical trial should discuss the treatment option with their mesothelioma specialist to determine if they’re eligible for a trial and if the experimental treatment is the best option for their specific case.
Side Effects and Risks of Keytruda
Side effects with Keytruda are typically mild, though quite common. One study from 2017 reported that 64% of their participants experienced adverse effects from the treatment. However, the most common side effects were fatigue and nausea, which were reported among 24% of patients. While more than half of patients in the study experienced side effects, no participants chose to discontinue treatment due to adverse effects, indicating to researchers that Keytruda is a tolerable treatment with low-toxicity.
- Dry mouth
- Joint pain
- Loss of appetite
While the common side effects are relatively mild among pleural mesothelioma patients treated with Keytruda, there are certain risks associated with any course of immunotherapy treatment. While the immunotherapy drugs work to attack the cancer cells within a patient's body, they may also erroneously attack healthy cells and negatively impact organ function.
- Dermatitis (inflammation of the skin)
- Colitis (inflammation of the colon)
- Hepatitis (inflammation of the liver)
- Hypothyroidism (underactive thyroid)
- Hypophysitis (inflammation of the pituitary gland)
- Interstitial nephritis (inflammation of the kidneys)
- Pneumonitis (inflammation of the lung walls)
- Uveitis (inflammation of the eye)
More rarely, there have been reports of minimal change disease (MCD) among pleural mesothelioma patients undergoing treatment with Keytruda. MCD is a kidney disease caused by nephrotic syndrome. Cancer patients with MCD lose protein through their urine. The condition presents with swelling and weight gain and cannot be diagnosed with a typical microscope. Pleural mesothelioma patients who present with MCD will most likely be advised to cease treatment with Keytruda and will be prescribed steroids to combat the MCD.
Knowing the potential of risk, both rare and common, is important for patients prior to beginning any treatment modality. For some mesothelioma patients, the benefits of treatment with Keytruda may outweigh potential risks. With no cure, and limited effective treatment options available to mesothelioma patients, the promise of a new treatment is a source of hope for those impacted by the disease.
Author: Linda Molinari
Editor in Chief, Mesothelioma Cancer AllianceRead about Linda
Reviewer: Annette Charlevois
Patient Support CoordinatorRead about Annette
Alley EW, Lopez J, et al. Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial. The Lancet Oncology. May 2017;18(5):623-630. doi: 10.1016/S1470-2045(17)30169-9
Bickel A, Koneth I, et al. Pembrolizumab-associated minimal change disease in a patient with malignant pleural mesothelioma. BMC Cancer. August 2016;16:656. doi: 10.1186/s12885-016-2718-y
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ClinicalTrials.gov. Study of Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-3475-028/KEYNOTE-28). NIH U.S. National Library of Medicine.
Kindler H, Theodore K, et al. OA13.02 Phase II Trial of Pembrolizumab in Patients with Malignant Mesothelioma (MM): Interim Analysis. Journal of Thoracic Oncology. January 2017: 12(1) suppl, S293–S294. doi: 10.1016/j.jtho.2016.11.301
Penn Medicine News. Pembrolizumab Shows Promise in Treatment of Mesothelioma. News Releases.