Pembrolizumab (Keytruda) for Mesothelioma

What Is Keytruda (Pembrolizumab)?

The immunotherapy drug Keytruda (pembrolizumab) has shown effectiveness in mesothelioma patients through clinical trials and the Merck Access Program. In May 2024, the FDA prioritized Keytruda for use in combination with chemotherapy as a frontline treatment for unresectable malignant pleural mesothelioma.

According to the FDA, the use of Keytruda with chemo may benefit patients with mesothelioma who are not eligible for surgery. The FDA’s move factors into account the Phase 2 and 3 IND.227/KEYNOTE-483 trial results.

Keytruda Information

Keytruda is a prescription medication administered via IV injection. It belongs to a class of immunotherapy drugs known as checkpoint inhibitors. 

Keytruda works best as a secondary treatment for mesothelioma patients whose cancer didn’t 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 3 weeks or 400 mg every 6 weeks. This recommendation 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.

Multiple clinical trials involving Keytruda to treat mesothelioma are ongoing worldwide. Most trials involve multimodal therapy combined with Keytruda and other treatments, such as surgery or radiation.

How Does Keytruda (Pembrolizumab)Work to Treat Mesothelioma?

Unlike chemotherapy or radiation therapy, Keytruda and other checkpoint inhibitors aim to boost the body’s natural defenses against cancer cells. Keytruda obstructs the PD-1 protein pathway, helping the immune system fight mesothelioma.

It blocks an interaction between PD-1 and another protein called PD-L1, which allows the immune system to recognize and attack mesothelioma cells. About 50% 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.

Side Effects of Keytruda (Pembrolizumab) for Mesothelioma

While essentially unmasking mesothelioma cells, Keytruda can also cause your immune system to attack normal organs and tissues in the body. This process affects the way normal cells work. 

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

Reported Keytruda Side Effects

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 Keytruda (Pembrolizumab)

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

Potential Serious Adverse Reactions

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

Some patients may experience adverse intravenous reactions, such as chills, dizziness, fever, itching or rash, 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 Keytruda (Pembrolizumab)?

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 levels are high in 20% to 40% of pleural mesothelioma patients, and these patients tend to experience the best clinical trial responses. PD-L1 also appears to be more common in non-epithelial mesothelioma tumors.

While the FDA is reviewing Keytruda with chemotherapy as a frontline treatment, Keytruda is currently available through a prescription as a second-line treatment for late-stage mesothelioma patients. It’s 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. However, it remains relatively ineffective as a long-term solution.

Encouraging Results from KEYNOTE-483 Trial

Results of the trial show that Keytruda combined with chemotherapy can boost overall survival rates compared to chemo alone. Adding Keytruda to the chemotherapy regimen reduced the risk of death by 21% compared to chemotherapy alone. 

Patients who received combination treatment showed an improved overall response rate of 62% compared to 38% in the group that only received chemotherapy. The combination treatment showed significant progression-free survival – a 20% benefit in the risk of progressing the disease or dying.

Keytruda’s FDA approval in 2020 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.

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