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 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 interaction between PD-1 and the PD-L1 protein 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 for up to two years or longer if effective and well-tolerated. Keytruda is 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 multiple clinical trials to date.
The KEYNOTE-028 clinial trial conducted in 13 different sites across six different countries was the first to show 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. Other clinical trials have shown results that have confirmed the success achieved in KEYNOTE-028. One 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.
More trials are still underway and results will continue to be reported.
Eligibility for Keytruda
Keytruda has now been included as a recommended therapy option in the National Comprehensive Cancer Network (NCCN) malignant pleural mesothelioma guidelines, meaning that patients can now receive immunotherapy drugs as a standard treatment option outside of a clinical trial. There are clinical trials involving Keytruda and other immunotherapies used in combination with other treatments that may represent a good option for some patients.
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)
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: Dr. James Stevenson
Medical Reviewer and Thoracic Medical OncologistRead about Dr. Stevenson
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
ClinicalTrials.gov. Pembrolizumab in Treating Patients With Malignant Mesothelioma. NIH U.S. National Library of Medicine.
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.