FDA Moving Keytruda Along in Approval Process for Mesothelioma

Years after the U.S. Food and Drug Administration (FDA) approved the immunotherapy combination Opdivo and Yervoy for mesothelioma, the FDA is strongly considering a major approval of Keytruda for mesothelioma.

Mesothelioma is a rare cancer diagnosed in 2,500-3,000 people in the U.S. each year. It is one of the rarest cancers and also one of the most aggressive.

Merck, the manufacturer of Keytruda (brand name for the immunotherapy drug pembrolizumab), announced recently the FDA is giving “priority review” to Keytruda in combination with standard mesothelioma chemotherapy. A decision from the FDA regarding approval, rejection or further review is expected by the end of 2024.

The therapy is being considered as a first-line treatment option for people with unresectable advanced or metastatic pleural mesothelioma. This type of mesothelioma forms in the lining of the lungs (called “the pleura”) and is associated with an average survival length of 10-14 months.

 

Current Treatment Options for Pleural Mesothelioma

People with pleural mesothelioma who do not receive any treatment have an average survival of less than one year. Mesothelioma treatment helps improve survival by at least a few precious months for patients.

Receiving just mesothelioma chemotherapy is associated with an average survival of 14-16 months. Surgery for pleural mesothelioma can help patients live for 2-3 years, and in some cases can lead to a survival of more than five years.

The FDA considers applications for approving immunotherapy due to the improved survival and quality of life. Immunotherapy for mesothelioma can improve survival and usually causes fewer severe side effects compared to chemotherapy.

 

What is Keytruda?

Keytruda is in a class of immunotherapy for cancer called “immune checkpoint inhibitors.” These immunotherapies block the activity of specific proteins to activate the immune system against the tumors.

Keytruda blocks the activity of the cancerous protein PD-L1. It is called a “PD-L1 immune checkpoint inhibitor.”

PD-L1 is a protein expressed on the surface of mesothelioma cells. The protein connects with and subdues the protein PD-1 on the surface of the immune system’s T cells, which are responsible for protecting the body from diseases such as cancer. PD-L1 subdues PD-1 and shuts the T cells off from attacking the cancer cells.

Keytruda and other PD-L1 inhibitors block the two proteins from connecting. The drug allows the T cells to remain active in the presence of mesothelioma tumor cells and attack the disease.

 

FDA Considering Keytruda for Larger Approval

Merck said the FDA’s priority review is based on data from a phase 3 clinical trial called KEYNOTE-483, which analyzed Keytruda with chemotherapy compared to chemotherapy alone. The trial included 440 people with unresectable advanced pleural mesothelioma

Keytruda with chemotherapy improved overall survival, progression-free survival, and the objective response rate. The median survival of Keytruda with chemotherapy is 17.3 months, whereas chemotherapy alone was 16 months.

Approximately 26% of people receiving Keytruda had progression-free survival – meaning no signs of cancer advancing or growing – through one year. Only 17% of people receiving chemotherapy had progression-free survival at one year.

Lastly, people receiving Keytruda had a 62% response rate. The chemotherapy group only had a 38% response rate.

 

FDA Approvals of Immunotherapy for Mesothelioma

The FDA approved Opdivo (brand name for nivolumab) and Yervoy (brand name for ipilimumab) for mesothelioma in October 2020 as a first-line treatment option for people with unresectable pleural mesothelioma.

This approval is the most significant one from the FDA involving immunotherapy for mesothelioma. The two immunotherapies are approved for use together, and the average survival for people receiving the treatment pairing 18 months.

The FDA approved Keytruda in June 2020 for a small subset of people with mesothelioma. The drug is approved for patients with high tumor mutational burden, meaning the tumor has a high volume of genetic mutations.

Malignant pleural mesothelioma patients have a high tumor mutational burden due to levels of the cancerous protein PD-L1. This high mutational burden also applies to some people with non-small-cell lung cancer.

 

Keytruda Approved for Lung Cancer

Keytruda is approved as a first-line treatment with chemotherapy for people with several types of non-small-cell lung cancer:

• Metastatic nonsquamous non-small-cell lung cancer with no EGFR or ALK genomic tumor aberrations
• Metastatic squamous non-small-cell lung cancer

Keytruda is also approved as a single agent first-line treatment option for people with:

• Stage 3, unresectable non-small-cell lung cancer expressing PD-L1 at a minimum level with no EGFR or ALK genomic tumor aberrations
• Non-small-cell lung cancer whose tumors express PD-L1 at a specific level with disease progression on or after platinum-containing chemotherapy
• Resectable non-small-cell lung cancer in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery
• Stage 1B, stage 2, or stage 3A resectable non-small-cell lung cancer following surgery and chemotherapy