Looking Beyond Clinical Trials for Mesothelioma Treatment

Clinical trial results should not always be the guiding force when a mesothelioma cancer patient and their medical team determine what therapy path to take, according to one recent study. A look at real-world populations might be just as important.

A research team at the University of Pennsylvania Department of Medicine has made the point with a retrospective, observational analysis of second-line treatment for pleural mesothelioma.

The analysis came on the heels of a multicenter clinical trial from the European Thoracic Oncology Platform that evaluated the efficacy of pembrolizumab (Keytruda), an immunotherapy drug, when compared to chemotherapy in a second-line setting for mesothelioma.

Despite high pretrial expectations, the use of pembrolizumab showed no survival advantage over the use of chemotherapy for mesothelioma in a second-line setting. Progression-free survival was only 2.5 months with pembrolizumab, compared to 3.4 months for chemotherapy. Median survival was 10.7 months and 12.4 months, respectively.

“Obviously, there is a lot of excellent work being done in the clinical trial space, especially with a rare disease and novel therapies like this,” Dr. Roger Kim, lead study author at the University of Pennsylvania, told The Mesothelioma Center at Asbestos.com. “But it is really important to assess those same kind of treatments in real-world populations. That may be the biggest take-home message from our study.”

Clinical Trials vs. Real-World Results

Mesothelioma clinical trials often involve carefully selected patients, many of whom are in a less-advanced stage of disease, healthier overall and able to meet specific criteria to qualify.

For this latest study, researchers took a multicenter retrospective look at 176 patients with advanced pleural mesothelioma who had received platinum-based chemotherapy initially and at least two lines of systemic therapy.

After relapse, 61 received chemotherapy and 115 received pembrolizumab or nivolumab, similar immunotherapy drugs, also known as immune checkpoint inhibitors. The results were considerably different.

Mesothelioma treatment with the immunotherapy drugs produced a median overall survival of 8.7 months, compared to only five months for those receiving chemotherapy. The estimated 12-month survival rate projection was 36.7% and 15.6%, respectively.

“We were able to demonstrate an increased benefit when compared to chemotherapy,” Kim said. “Patients who received chemotherapy – in our real-world population – fared much poorer than in the clinical trial, which is reflective of the older, generally sicker populations of patients we see in the clinic in the real world.”

Treatments Benefit Patients With Advanced Disease 

In contrast to the European clinical trial, the retrospective study found that the immune checkpoint inhibitors benefited those with a more advanced stage of mesothelioma. Lung Cancer published the study findings in late 2021.

Patients in the latest study – the real-world population – were older (median age 75) than in the clinical trial (70). There also was a much lower percentage of patients with the more treatable epithelioid histology.

They generally had a more limited life expectancy, according to study authors. More than 10% had undergone aggressive surgery before even starting the first-line systemic therapy.

“Different baseline characteristics, different patient populations, may perform differently with the same exact medications,” Kim said. “It’s important to know.”

Prior studies had suggested a potentially larger benefit from the immune checkpoint inhibitor drugs for those with a tougher-to-treat histology.

“That our outcomes differed from those reported in the clinical trial highlights the importance of assessing real-world evidence when evaluating novel therapies in populations that differ from those included in clinical trials,” the study concluded.

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