Mesothelioma and Keytruda

Keytruda, also known as pembrolizumab, is a type of immunotherapy drug that has shown promise in extending the life expectancy of mesothelioma patients.

Key Points

  • 1

    Keytruda is a type of immunotherapy drug.

  • 2

    Keytruda and immunotherapy have become more standard in mesothelioma treatment.

  • 3

    Immunotherapy may be an option for patients who don’t respond to standard treatments.

  • 4

    Keytruda has shown improved survival among mesothelioma patients in clinical trials.

Keytruda is an immunotherapy drug that is designed to boost the immune system, causing an anti-cancer effect that can help the body kill cancer cells, ultimately working to treat cancers like malignant mesothelioma. The drug, developed by Merck, has shown promise in improving quality of life and overall survival for mesothelioma patients in clinical trials and has recently become a more standard treatment option for mesothelioma after showing success in these various studies. Keytruda is approved by the U.S. Food and Drug Administration (FDA) as a first-line treatment for non-small cell lung cancer (NSCLC), melanoma, Merkel cell carcinoma (MCC) and other cancers, and researchers hope it will become FDA approved for mesothelioma.

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How Keytruda Treats Mesothelioma

Keytruda works with the body’s immune system for cancer treatment. As an immune checkpoint inhibitor, Keytruda targets checkpoints that prevent immune cells from attacking and killing cancer cells. T-cells, which are used by the body to detect and fight infections, are sometimes tricked by the PD-L1 (programmed death ligand-1) protein found on normal and cancerous cells. Keytruda inhibits the PD-1 immune checkpoint from identifying cancerous cells as normal cells in order to help the immune system recognize and fight them.

Keytruda is administered through an IV over 30-minute periods every three weeks. Patients are allowed to receive chemotherapy treatment with Keytruda, which can be administered on the same day, but Keytruda should be given first. For a while, Keytruda and other immunotherapy drugs were only available through clinical trials. Recently, however, the National Cancer Comprehensive Network (NCCN) added a recommendation of Keytruda and Opdivo, another checkpoint inhibitor, as a treatment for pleural mesothelioma patients who had previously undergone chemotherapy. As a result, Keytruda and immunotherapy are becoming more widely used in mesothelioma treatment plans.

Patient Success With Keytruda

Keytruda has shown promise in clinical trials as a treatment for patients whose mesothelioma doesn’t respond to standard treatments, which helped lead to the NCCN’s recommendation. However, though the drug and other immunotherapies are now more widely available, researchers are continuing to test efficacy and different combinations in clinical trials to find the best results and hopefully receive FDA approval for mesothelioma.

One clinical trial, KEYNOTE-028, studied 25 participants with malignant pleural mesothelioma from 13 centers in six countries. The patients were given the drug every two weeks for two years, until the tumor progressed or until the toxicity of the drug became intolerable. The participants were assessed every eight weeks for solid tumor growth and overall health. Researchers concluded that five patients had a partial response to the drug and 14 of 25 participants saw tumor reduction. The overall disease control rate from this study was 76%, with a median progression-free survival of 6.2 months and average overall survival of 18 months.

A phase II clinical trial is expected to be completed in 2020, which will better determine survival rates for patients with mesothelioma and may eventually lead to FDA approval of the drug for mesothelioma treatment.

In another clinical trial conducted in Australia and Switzerland, 93 malignant pleural mesothelioma patients were treated with pembrolizumab as a palliative treatment. Patients were given different doses based on their individual case, and it was administered as a first- or second-line treatment. Of the participants, 68 had epithelioid mesothelioma, 15 had sarcomatoid mesothelioma and 10 had mixed or biphasic mesothelioma. All patients were assessed with an Eastern Cooperative Oncology Group (ECOG) performance status to rate their quality of life. The ECOG performance status uses a scale of 0 – 5, with 0 representing a patient who is fully active and able to perform their usual daily tasks, while 5 marks a patient who has passed away. Ratings of 1 – 3 represent patients with increasingly limited mobility and energy to complete their daily tasks.

Researchers found a range of scores in their ECOG data:

  • 11 patients had a score of 0
  • 55 patients had a score of 1
  • 27 patients had a score of 2 or greater

Researchers also documented the presence of PD-L1 in 71% of the participants and found:

  • 68% of the available samples were PD-L1 negative
  • 18% had intermediate levels of PD-L1
  • 14% were considered high amounts of PD-L1

Overall, the study tested pembrolizumab as a palliative treatment for three months on average with a median followup time of nine months. At the end of treatment, the researchers noted an overall response rate of 18%, with a disease control rate of 48%, meaning these patients achieved either stable disease, partial remission or complete remission. Stable disease means the mesothelioma did not grow or spread during treatment, while partial or complete remission indicate a reduction in tumor size and growth. Of those who were tested, individuals with high PD-L1 expression had a better overall response rate to the drug at 44% compared to participants with intermediate and low PD-L1 expression, who responded at 42% and 11%, respectively.

The study concluded that the median overall survival for all patients in the study was 7.2 months, with a 6-month progression-free survival rate of 26%. Researchers also noted a median overall survival of 10.2 months for patients with low ECOG scores at the beginning of the trial.

Other checkpoint inhibitors like Opdivo (nivolumab), which also target the PD-1 protein in the body, have shown similar promising results in clinical trials. One trial with Opdivo concluded that 68% of participants experienced disease control, which means that their cancer did not spread or worsen during treatment. Opdivo and Keytruda have been tested frequently together in clinical trials and shown promise in improving quality of life and life expectancy in mesothelioma patients.

Keytruda Side Effects and Risks

The side effects for Keytruda are often mild, but the drug can also create potentially dangerous health concerns for patients. Researchers have seen a range of common symptoms in clinical trials. In one recent clinical trial, more than half of participants experienced side effects, with symptoms of fatigue and nausea experienced by 24% of patients, while 20% experienced joint pain. Other common side effects include shortness of breath, a decrease in appetite, itching, fever, cough and constipation. Some patients may experience side effects associated with chemotherapy in combination with Keytruda, such as hair loss, trouble breathing and inflammation of the nerves.

Common Side Effects
  • Anemia
  • Cough
  • Constipation
  • Decrease in appetite
  • Diarrhea
  • Fever
  • Fatigue
  • Itching
  • Nausea
  • Shortness of breath
Potential Serious Side Effects
  • Colitis
  • Hepatitis and liver problems
  • Hormone gland problems
  • Infusion (IV) reactions
  • Nephritis
  • Pneumonia and other lung problems
  • Stevens-Johnson syndrome (SJS)
  • Toxic epidermal necrolysis (TEN)

Taking an immunotherapy drug can also cause other side effects that may be more serious. Since immunotherapy drugs use the body’s immune system to attack cancerous cells, the body may also attack healthy cells and organs, resulting in complications. Although they are less common, immune-mediated rashes like Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) can occur.

Problems with other organs can also occur as a result of taking an immunotherapy drug, such as eyesight changes, joint pain, muscle weakness, irregular heartbeat and chest pain. It is important that patients assess the risks of Keytruda and consult with a medical professional if they experience any symptoms while taking the medication.

Eligibility for Treatment with Keytruda

Keytruda is available in clinical trials for mesothelioma patients, but the National Comprehensive Cancer Network (NCCN) has also recommended immunotherapy as a first-line treatment for malignant pleural mesothelioma patients. This means that patients may now have access to clinical trial level treatments with only a medical professional’s recommendation. Cancer patients should consult a medical professional to see if they may be eligible to add Keytruda to their treatment plan or participate in a clinical trial involving Keytruda, as trials through the National Cancer Institute (NCI) have specific qualifications for participants, such as having undergone chemotherapy prior to seeking out alternative treatment.