Pembrolizumab (Keytruda) for Mesothelioma

What Is Pembrolizumab (Keytruda)?

The immunotherapy drug pembrolizumab (Keytruda) has shown effectiveness in mesothelioma patients through clinical trials and the Merck Access Program. 

In June 2020, the U.S. Food and Drug Administration approved its use as a second-line treatment for cancer patients with high tumor mutation burden, or TMB-H, including late-stage mesothelioma patients.

The FDA concluded that late-stage mesothelioma patients whose disease has progressed following prior treatment and who have no viable alternative options are eligible to receive Keytruda.

Patients must also undergo an FDA-approved test to show if they have a high tumor mutation burden. This test ensures that physicians only prescribe Keytruda to patients who will receive the most benefit.

More than half of pleural mesothelioma patients in a completed clinical trial experienced initial tumor reduction during treatment, and 40% had a partial response or stable disease. The average overall survival was 18 months, with several living two years or more following treatment.

More than a dozen clinical trials involving Keytruda for mesothelioma are ongoing or actively recruiting participants. Most of these trials involve multimodal therapy that combines Keytruda with another therapy such as surgery or radiation therapy. 

How Does Pembrolizumab (Keytruda) Work to Treat Mesothelioma?

Keytruda belongs to a class of immunotherapy drugs known as checkpoint inhibitors. Unlike chemotherapy or radiation therapy, Keytruda and other checkpoint inhibitors aim to boost the body’s natural defenses against cancer cells. 

Keytruda helps the immune system fight mesothelioma by obstructing the PD-1 protein pathway. It works by blocking an interaction between PD-1 and another protein called PD-L1, which allows the immune system to recognize mesothelioma cells and attack them. About half of mesothelioma cells carry high expressions of PD-L1 to hide from the immune system, which is why Keytruda works for some mesothelioma patients.

Doctors and researchers are now using Keytruda in combination with traditional mesothelioma treatments such as surgery and chemotherapy with platinum-based drugs. Many patients are turning to immunotherapy drugs after chemotherapy stops working, which it often does.

It seems to work well in certain cases. We still don’t have enough data to say for sure, but yes, [Keytruda] could become the next big thing for mesothelioma.

Dr. Tawee Tanvetyanon

Oncologist at the Moffitt Cancer Center in Tampa

Keytruda is a prescription medication administered by IV injection. Keytruda is usually administered as a secondary treatment for mesothelioma patients whose cancer did not respond or recurred after primary treatment such as surgery, radiation or chemotherapy. Like many chemotherapy regimens, treatments with Keytruda are usually given over 30-minute sessions every three weeks.

The recommended Keytruda dosage regimen for TMB-H solid tumors in adults is 200 mg every three weeks or 400 mg every six weeks.

This may vary for mesothelioma patients accessing the immunotherapy drug through a clinical trial or the Merck Access Program. Your doctor or the researcher leading the study will determine the appropriate dosage and how long a patient should stay on Keytruda.

Side Effects of Pembrolizumab (Keytruda) for Mesothelioma

While essentially unmasking mesothelioma cells, Keytruda can also cause your immune system to attack normal organs and tissues in many areas of the body, affecting the way they work.

This can lead to serious and sometimes life-threatening side effects. However, side effects of Keytruda are minimal compared to those for cancer patients undergoing chemotherapy.

Pleural mesothelioma patients who took part in a Keytruda clinical trial at the Penn Medicine Abramson Cancer Center reported only dry mouth, fatigue, nausea and loss of appetite. None of the patients had to stop treatment because of side effects.

In the 2021 published results of the ongoing phase 2 KEYNOTE-158 clinical trial, which includes mesothelioma patients, 69% of participants who received Keytruda reported treatment-related side effects. Serious adverse events associated with treatment occurred in 12% of patients.

Serious Side Effects of Pembrolizumab (Keytruda)

In rare cases, Keytruda can cause a serious immune reaction. Organs typically affected by these reactions include the lungs, intestinal tract, liver, kidneys and certain hormone glands.

Examples of hormone gland problems include hair loss, muscle aches, rapid heartbeat, recurring headaches and weight loss. Kidney problems may include nephritis (inflammation of the kidneys) and kidney failure.

Some patients may experience adverse intravenous reactions, such as chills, dizziness, fever, itching or rash and shortness of breath or wheezing. Mesothelioma patients taking Keytruda should be aware of these side effects and alert their doctor immediately if they experience these symptoms.

Are All Mesothelioma Patients Eligible for Pembrolizumab (Keytruda)?

Mesothelioma patients who have a high tumor mutation burden are eligible for Keytruda. They must also have recurring cancer after undergoing a first round of treatment.

PD-L1 is expressed in 20% to 40% of pleural mesothelioma patients, and these patients tend to experience the best responses in clinical trials. PD-L1 also appears to be more common in nonepithelial mesothelioma tumors.

Keytruda is available through a prescription as a second-line treatment for late-stage mesothelioma patients. It is also available through clinical trials with varying eligibility requirements.

A combination of surgery, chemotherapy and radiation therapy is still the standard first-line treatment for early-stage mesothelioma, but it remains relatively ineffective as a long-term solution.

Success Rate of Pembrolizumab (Keytruda) for Mesothelioma

Studies show about 8.5% to 22% of patients with pleural mesothelioma respond to Keytruda. Overall survival has ranged from 10 months to 18.7 months (about a year and a half) in patients with PD-L1–positive mesothelioma.

In 2022, results from a trial known as PROMISE-meso showed that standard chemotherapy outperformed Keytruda. Overall survival was 10.7 months for participants on Keytruda compared to 12.4 months for patients on chemotherapy.

Results from a 2020 study known as KEYNOTE-158 showed an impressive duration of response lasting 14.3 months in pleural patients with a partial response.

Clinical trials investigating Keytruda for mesothelioma are ongoing, and many of them combine the drug with other treatments in hopes of finding the right combination to significantly improve survival.

This therapy has given me a new window. It may not save my life, but it’s certainly buying me some valuable time.

Walter Merth

Diagnosed with pleural mesothelioma in 2015

Keytruda’s FDA approval as a second-line therapy for cancer patients with high tumor mutation burden, including mesothelioma patients, followed approvals for its use with melanoma, colorectal cancer and lung cancer. Many in the medical community believe the drug represents a potential for future advancements in the long-term management of mesothelioma.