How Pembrolizumab (Keytruda®) Treats Mesothelioma
Keytruda® (pembrolizumab) is an immunotherapy drug categorized as an immune checkpoint inhibitor, a type of monoclonal antibody. The drug works by blocking the PD-1 protein on immune cells (T 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 live. 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.
Which Cancers Can Pembrolizumab (Keytruda®) Treat?
Keytruda® earned its first approval from the U.S. Food and Drug Administration (FDA) in 2014. At the time, the drug approval only allowed treatment of certain types of melanoma. However, positive results in clinical trials have expanded indications for Keytruda®. It now carries approval for more than 10 different types of cancer.
Mesothelioma is not the only asbestos-related cancer Keytruda® can treat. This immunotherapy drug can also treat some forms of non-small cell lung cancer (NSCLC). Doctors can use Keytruda® alongside platinum and pemetrexed chemotherapy for qualified cases of NSCLC.
One of Keytruda®’s approved uses may cover some mesothelioma patients. Doctors can prescribe Keytruda® for patients whose cancers fall into a category called TMB-H.
TMB-H stands for tumor mutational burden-high. TMB-H means that tumor cells have a high number of genetic mutations.
Some mesothelioma tumors fall into the TMB-H category. Doctors may prescribe Keytruda® in such cases.
The Pembrolizumab (Keytruda®) Treatment Process
Keytruda® is administered via IV (intravenous therapy) for 30-minute increments every three weeks. Courses of treatment may 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.
Survival After Pembrolizumab (Keytruda®) for Mesothelioma
Several clinical studies have evaluated the effect of Keytruda® (pembrolizumab) on mesothelioma prognosis. Median survival for pleural mesothelioma patients receiving Keytruda® ranges from 10 to 18 months.
Mesothelioma Survival in the KEYNOTE-028 Clinical Trial
The KEYNOTE-028 clinical trial involved 13 different sites across six countries. It was one of the earliest studies to report success in treating malignant pleural mesothelioma with Keytruda®. Study participants had previously received chemotherapy or did not qualify for standard treatment. Researchers reported several encouraging results:
- 56% of patients experienced a reduction in tumor size.
- Patients experienced about five months with no tumor progression.
- Median overall survival reached 18 months.
This median survival result falls among the best reported for second-line mesothelioma therapy. The success of this early trial may have motivated researchers to continue studying this drug.
Mesothelioma Survival After Pembrolizumab (Keytruda®) Combination Immunotherapy
Another mesothelioma clinical trial investigated Keytruda® as part of a combination treatment. The combination extended survival to nearly two years. Researchers achieved this by combining Keytruda® with another immunotherapy: CAR T cells.
CAR T-cell therapy is a new approach to cancer treatment. Doctors use a patient’s own immune cells to create cancer-fighting cells called CAR T cells. Once they have enough, doctors give the CAR T cells back to the patient. The CAR T cells can then identify and attack cancer cells.
Prior to the study, participants had already received at least one form of mesothelioma treatment. After enrolling, pleural mesothelioma patients first underwent CAR T-cell therapy. Weeks later, they received Keytruda®. Researchers found Keytruda® helped the CAR T cells fight cancer.
Patients receiving Keytruda® with CAR T cells had a median survival of 23.9 months. Notably, more than 70% of the patients in this study had late-stage mesothelioma. Mesothelioma life expectancy in later stages ranges from 12 to 16 months. This means CAR T cells and Keytruda® may have improved survival by a year for these patients.
Mesothelioma and Pembrolizumab (Keytruda®) Research Is Ongoing
The efficacy of Keytruda® for mesothelioma is still being tested, with various ongoing studies. As of March 2022, several mesothelioma clinical trials included Keytruda® as part of their treatment approach.
In some studies, Keytruda® will provide one part of a multimodal mesothelioma treatment. This may prove beneficial, as multimodal treatment has come the closest to a mesothelioma cure.
Resources for Mesothelioma Patients
Eligibility for Pembrolizumab (Keytruda®)
Keytruda® (pembrolizumab) has FDA approval for use in patients with TMB-H classified tumors. This means mesothelioma patients with the following characteristics may qualify for Keytruda® treatment:
- Doctors consider the patient’s case inoperable.
- The patient has no other satisfactory treatment options.
- The patient has received another treatment first, and the cancer has progressed despite treatment.
- The patient’s tumor falls into the TMB-H category. TMB-H status means the tumor has a high number of genetic mutations.
Keytruda® has not achieved approval in mesothelioma specifically. Still, some experts see a role for the checkpoint inhibitor in some mesothelioma cases. For instance, the National Comprehensive Cancer Network (NCCN) includes Keytruda® in its treatment guidelines. NCCN recommends Keytruda® as a potential second-line treatment for pleural mesothelioma.
Any mesothelioma patient considering Keytruda® should discuss their options with a doctor. A mesothelioma doctor can help them understand the risks and benefits of available therapies. Together, the patient and doctor can devise the best approach for the patient’s unique situation.
04. Side Effects
Side Effects and Risks of Pembrolizumab (Keytruda®)
Side effects with Keytruda® (pembrolizumab) are typically mild, though common. In the KEYNOTE-028 trial, 64% of mesothelioma patients who received Keytruda® reported at least one side effect. The most common side effects were nausea and fatigue, reported by 24% of patients. Other common Keytruda® side effects include joint stiffness, itching, decreased appetite and dry mouth.
None of the study patients discontinued treatment due to severe side effects.
Common Pembrolizumab (Keytruda®) Side Effects
- Dry mouth
- Joint pain
- Loss of appetite
The common side effects are relatively mild among pleural mesothelioma patients treated with Keytruda®. However, some patients with other cancers have experienced more serious reactions.
In certain cases, Keytruda® patients have had immune-mediated responses or autoimmune reactions. This means Keytruda® may allow the patient’s immune system to attack healthy tissues or cause other problems. Such reactions are considered uncommon and may resolve after discontinuing treatment.
Autoimmune Reactions to Pembrolizumab (Keytruda®)
- Colitis (inflammation of the colon)
- Dermatitis (inflammation of the skin)
- Hepatitis (inflammation of the liver)
- Hypophysitis (inflammation of the pituitary gland)
- Hypothyroidism (underactive thyroid)
- Nephritis (inflammation of the kidneys)
- Pneumonitis (inflammation of the lung walls)
- Uveitis (inflammation of the eye)
Any patient interested in Keytruda® should discuss it with an oncologist. Mesothelioma patients can discuss side effects and advantages with their doctor. A mesothelioma expert can help patients weigh the benefits and risks of standard and emerging treatments.