Could Keytruda® and Chemotherapy Become New Standard of Care for Mesothelioma?

Keytruda®and Chemotherapy for Mesothelioma

During this year’s American Society of Clinical Oncology (ASCO) Annual Meeting, researchers presented the results of a phase 3 global clinical trial called KEYNOTE-407. The study’s data concluded that the combination of Keytruda® (pembrolizumab) and standard platinum-based chemotherapy should be the new first-line treatment for metastatic non-small cell lung cancer (NSCLC), which could also mean changes ahead for mesothelioma treatment.

Researchers found that with just the standard chemotherapy combination of carboplatin and paclitaxel/nab-paclitaxel, median overall survival for metastatic NSCLC reached about 11.3 months. When they paired chemotherapy with Keytruda®, follow-ups showed overall survival extended to 15.9 months on average across all the lung cancer patient subgroups in the trial, including in those with low PD-L1 expression.

Cancer research has linked the protein PD-L1 to several kinds of cancers, including mesothelioma. The protein is expressed on normal cells and can also be found on cancer cells, which can trick the immune system and allow the dangerous cells to escape attack. PD-L1 is often targeted by different kinds of immunotherapy (sometimes called anti-PD-1), such as Keytruda®. By blocking the signal between PD-L1 and PD-1, which binds to the PD-L1 protein to signal healthy cells to the immune system, the body can properly recognize and kill cancer cells.

The positive results from KEYNOTE-407 correlate to a previous study that focused on another type of lung cancer, metastatic nonsquamous NSCLC. Researchers found adding Keytruda® to the conventional chemotherapy regime significantly increased life expectancy for patients with this type of lung cancer, as well. Progression-free survival also improved in both trials. Patients with metastatic squamous NSCLC experienced an improvement from 4.8 months to 6.4 months on average.

“This trial is clearly a win,” Charles G. Drake, MD, PhD, of the Columbia University Herbert Irving Comprehensive Cancer Center said during the panel. Dr. Drake further stated that with the success of both of these trials, the chemotherapy + Keytruda® combination will become a new frontline standard of care.

This study is also important for other types of cancers, namely mesothelioma. Though Keytruda® and other immunotherapies have yet to be FDA approved for the rare cancer, these therapies have already shown success in various clinical trials in extending survival for numerous patients, including those with classical Hodgkin lymphoma, head and neck squamous cell carcinoma (HNSCC), and certain advanced cancers like melanoma and metastatic urothelial carcinoma. Many advanced NSCLC clinical trials are also often applied to mesothelioma, as the disease progressions are rather similar.

The current standard of care for mesothelioma is also a combination chemotherapy treatment of Alimta® and cisplatin, which hasn’t changed in years. With the success of KEYNOTE-407 and other trials, researchers hope the same methodology can be applied to other cancers like mesothelioma, potentially updating the standard treatment options and improving survival.