Keytruda, the brand name for pembrolizumab, has shown effectiveness with many patients through clinical trials and the Merck Access Program. As of June 2020, the U.S. Food and Drug Administration approved its use for a subset of mesothelioma patients as a second-line treatment.
The FDA has outlined that mesothelioma patients with advanced or metastatic disease who have progressed following prior treatment and have no viable alternative options are eligible to receive Keytruda.
Eligible patients must also undergo an FDA-approved test to show if they have a high tumor mutation burden, or TMB-H. This test ensures that physicians only prescribe Keytruda to patients who will receive the most benefit.
In May 2017, the FDA approved Keytruda in combination with chemotherapy as a first-line treatment for metastatic non-small cell lung cancer. Keytruda is also FDA-approved for the treatment of melanoma, specific subsets of colorectal cancer, head and neck cancers, metastatic bladder cancer and a few other malignancies.
A multicenter phase II clinical trial is currently underway involving a combination of Keytruda and the immunotherapy drug CRS-207, which is a genetically engineered version of the Listeria virus.
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 TanvetyanonOncologist at the Moffitt Cancer Center in Tampa
Keytruda has already shown its effectiveness individually with some mesothelioma patients.
More than half of pleural mesothelioma patients involved in an ongoing clinical trial experienced initial tumor reduction during treatment and an average time before progression of six months. The average overall survival for those patients was 18 months, with several living two years or more following treatment.
|Dosage||2 mg/kg every three weeks|
|Medical Code||J9271, C9027|
|Drug Class||Monoclonal antibody|
|Medical Studies||Pembrolizumab in Treating Patients with Malignant Mesothelioma|
|FDA Warning||Pneumonitis, colitis, hepatitis, hormone gland problems, kidney problems, anemia, skin rash, muscle or joint pain, muscle weakness, changes in eyesight|
How Does Keytruda Work?
Keytruda belongs to a class of immunotherapy drugs known as checkpoint inhibitors, which allow the immune system to fight cancer by blocking the PD-1 pathway.
Cancer cells use this pathway to hide from T cells, a type of white blood cell released by the immune system to attack damaged or diseased cells.
Scientists have found that many cancer cells carry proteins that act like masks, allowing them to blend in with healthy cells. This is often the reason why a patient’s own immune system is unable to recognize and fight off the abnormal malignant growth. Many cancer cells, including malignant mesothelioma cells, carry high expressions of the PD-L1 protein to carry out this deception
When T cells use the PD-1 protein to latch onto PD-L1 proteins on the surface of cancer cells, they’re fooled into thinking the cancer cells are healthy and move on to patrol the rest of the body for disease and infection. This allows the cancer cells to multiply and spread without an immune response.
Unlike chemotherapy or radiation therapy, Keytruda and other checkpoint inhibitors aim to boost the body’s natural defenses against cancer cells. By blocking the PD-1 and PD-L1 interaction, Keytruda allows the immune system to recognize mesothelioma as foreign and attack those cells.
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.
Keytruda is a prescription medicine administered by an intravenous (IV) injection. Similar to 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 is 200 mg every three weeks or 400 mg every six weeks for adults.
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 Keytruda for Mesothelioma
- Loss of appetite
- Dry mouth
- Low red blood cell count (anemia)
- Shortness of breath
- Pain in muscles, bones or joints
While essentially unmasking cancer 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 and other checkpoint inhibitors are minimal compared to cancer patients taking chemotherapy.
Pleural mesothelioma patients who took part in a Keytruda clinical trial at the Abramson Cancer Center at Penn Medicine reported only dry mouth, fatigue, nausea and loss of appetite. None of the patients had to stop treatment because of side effects.
In the clinical trial that led to the approval of Keytruda for first-line treatment of NSCLC, the most common side effects were nausea, fatigue and constipation. Patients who received Keytruda in combination with chemotherapy did see a 13 percent increase in the chance of serious side effects. Acute kidney problems were the most common.
Serious Side Effects of 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.
Some of the most serious adverse reactions include:
- Pneumonia: Shortness of breath, chest pain and new or worsening cough
- Colitis: Inflammatory infection of the colon that causes bloody or black stools, severe abdominal pain and possible tears or holes in the intestine
- Hepatitis: Inflammation of the liver characterized by yellowing of the skin, dark urine and pain in the right side of your abdomen
- Hormone Gland Problems: Can lead to hair loss, muscle aches, rapid heartbeat, recurring headaches and weight loss
- Kidney Problems: Including nephritis (inflammation of the kidneys) and kidney failure
Some patients may experience adverse IV reactions, such as chills, dizziness, fever, itching or rash and a 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.
History and Promising Results
The first FDA approval for Keytruda came in 2014 for the treatment of melanoma, which is a type of skin cancer. Former U.S. President Jimmy Carter credited the immunotherapy drug for stopping the cancer that had spread to his brain.
In 2015, the FDA approved Keytruda for colorectal cancer. The agency then approved the drug for certain lung cancers, but only as a single agent and only with tumors that expressed the PD-L1 protein.
The expanded 2017 approval for NSCLC is groundbreaking because it no longer requires the need for PD-L1 and allows using Keytruda as a first-line treatment alongside chemotherapy.
PD-L1 is typically expressed in about half of mesothelioma patients. A combination of surgery, chemotherapy and radiation therapy is still the standard first-line treatment of mesothelioma, but it remains relatively ineffective as a long-term solution.
Keytruda’s latest FDA approval is the first second-line therapy for late-stage mesothelioma patients. Many in the medical community believe the drug represents a potential for future advancements in the long-term management of mesothelioma.
In the meantime, mesothelioma survivors, such as Walter Merth and Mavis Nye, credit experimental Keytruda trials as the reason for their longevity. Merth started taking the drug in early 2016 as part of the Merck Access Program.
This therapy has given me a new window. It may not save my life, but it’s certainly buying me some valuable time.Walter MerthDiagnosed with pleural mesothelioma in 2015
When Nye was diagnosed with pleural mesothelioma in June 2009, doctors gave her a life expectancy of three months. She began taking Keytruda in May 2014 in a U.K. clinical trial. By April 2016, her doctors reported a “complete response.”
In an ongoing clinical trial involving 13 research sites covering six countries, 56 percent of mesothelioma patients experienced tumor reduction. All patients had previously received chemotherapy and were experiencing disease progression. After treatment with Keytruda, patients experienced a median progression-free period of six months.
“This study provides evidence that some patients [with mesothelioma] can have long-term disease control with this drug, which we haven’t seen before,” Dr. Evan Alley, chief of hematology and medical oncology at Penn Presbyterian Medical Center, told Asbestos.com. “We need to better understand what we can do next to make immunotherapy more effective for more patients.”
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