Latest Keytruda Study Shows Limited Results for Most Mesothelioma Patients

Results of the latest Keytruda study show the drug works well for a select few mesothelioma patients, but not well at all for most others.

Keytruda is the brand name for pembrolizumab. It is a type of immunotherapy drug. Early studies suggested that Keytuda might offer real hope for people with the aggressive cancer, malignant pleural mesothelioma. 

But the latest Keytruda study shows most patients do not have lasting results with this treatment. That is especially true for patients whose cells do not express high levels of the protein PD-1.

How the Latest Keytruda Study Worked

Keytruda is an immunotherapy drug. It works by activating the immune system. Mesothelioma cells can use a protein called PD-1 to protect themselves from immune system attack. Keytruda undermines this defense mechanism by neutralizing PD-1 activity.

The latest Keytruda study was called KEYNOTE-158. It enrolled 118 pleural mesothelioma patients between February and August 2016. These patients came from 35 hospitals in 14 countries. 

Study participants received 200 mg of intravenous Keytruda every three weeks. They could have up to 35 cycles of the drug. To track their tumor progression, patients had imaging studies every 9 weeks for the first year. Imaging tapered back to once every three months after that.

The study asked a series of questions including:

• How safe is the treatment?
• Which patients does it work for?
• Which patients does it not work for?
• When it does work, how long do the results last?
• When it does not work, why not?

Mixed Findings on Pembrolizumab

Of the 118 mesothelioma patients enrolled in the latest Keytruda study, only ten (8%) had an objective response. The good news is that, for six of those patients, the response lasted for a median of 17.7 months. This is significant because pleural mesothelioma is often fatal in 9 to 12 months. 

The six patients who had the best response were those with higher levels of PD-1. Four PD-1 negative patients also responded to Keytruda. But their effects did not last as long. The median duration of response for these patients was just 10.2 months.

Sixteen percent of patients (19) had serious treatment-related side effects from Keytruda. The most common problems were inflammation of the colon, inflammation of the lungs or low blood sodium. One patient died.

By the end of the latest Keytruda study, only 6 of the 118 patients were still taking the drug. Most had stopped because their mesothelioma came back. 

The authors conclude that Keytruda still can work for some pleural mesothelioma patients. But it is difficult to predict which patients will benefit. 

“Our data support the programmed death 1 (PD-1) and PD-L1 pathway as a potential therapeutic target in some patients with previously treated mesothelioma,” writes lead author Timothy Yap, MD, of MD Anderson Cancer Center. “But biomarkers that can effectively identify such patients are yet to be elucidated.”

Source:

Yap, et al, “Efficacy and safety of pembrolizumab in patients with advanced mesothelioma in the open-label, single-arm, phase 2 KEYNOTE-158 study”, April 6, 2021, https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(20)30515-4/fulltext