Researchers at the European Thoracic Oncology Platform (ETOP) didn’t get the results they hoped for after a recently completed phase 3 trial for mesothelioma treatment.
The randomized trial compared two different treatments involving pembrolizumab, or Keytruda, with standard chemotherapy for patients with progressive malignant pleural mesothelioma. Results from phase 2 trials were promising, but the current study didn’t have the same positive outcome.
The goal of this phase 3 trial, called PROMISE-meso, was to improve the performance of single-agent immunotherapy as a second-line treatment for patients who did not have success with the first round of standard chemotherapy drugs.
The ETOP presented its findings in late September, in Barcelona, at the annual ESMO Congress. Lead study author Sanjay Popat, Ph.D., announced Keytruda didn’t change disease outcomes in any study subjects.
Keytruda didn’t delay the progression of mesothelioma or improve patient survival. There were no significant differences between patients who received either Keytruda or standard chemotherapy.
Study Design: Pembrolizumab and Chemotherapy
The standard treatment for mesothelioma patients is a combination of Alimta (pemetrexed) and platinum-based chemotherapy drugs (cisplatin or carboplatin).
PROMISE-meso was the first randomized trial that compared progression-free survival between an immunotherapy drug and first-line chemotherapy for malignant mesothelioma patients.
The FDA has previously approved Keytruda as a treatment for several advanced cancers like non-small cell lung cancer, but not mesothelioma.
Malignant mesothelioma tumors consist of cells that often contain high levels of PD-L1, a type of protein found in the body’s immune cells.
Researchers tried to use Keytruda to block the PD-1 and PD-L1 pathway, which would allow the patient’s immune system to recognize and attack mesothelioma cells.
Trial participants were eligible for Keytruda after showing signs of high levels of PD-L1, though Keytruda worked better in patients with low levels of PD-L1.
Trial participants consisted of advanced mesothelioma patients who previously failed to show improvement after receiving platinum-based chemotherapy. Their disease progression must have been measurable, based on available tumor tissue samples.
The trial consisted of 144 randomized mesothelioma patients. Participants received either Keytruda or a standard chemotherapy drug, gemcitabine or vinorelbine.
Participants in the control group who received standard chemotherapy were able to switch to Keytruda if their mesothelioma progressed, or spread, during the trial.
In 22 percent of patients, Keytruda reduced tumor size compared to just six percent of patients receiving the other chemotherapy drugs.
While patients showed some response to Keytruda — nearly four times more than chemotherapy — the drug did not delay tumor growth or improve survival.
The median overall survival for Keytruda was 10.7 months. The median overall survival for chemotherapy was 11.7 months.
PROMISE-meso and other clinical trials involving immunotherapy drugs have shown short-lived results, meaning patients seemed to respond well at first, but it didn’t last.
Clinical Trial Brings New Outlook
While PROMISE-meso did not bring positive results, researchers now have a better understanding of the effects of this immunotherapy drug.
There aren’t many treatment options for mesothelioma patients. When patients relapse or fail to respond to platinum-based chemotherapy, they often run out of options.
Keytruda did not prove to be better than standard chemotherapy. However, researchers believe the immunotherapy drug could be an alternative for some patients who don’t benefit from standard platinum-based treatments.
The trial also provided researchers new hope for the combination of immunotherapy and chemotherapy as a beneficial first-line treatment for malignant mesothelioma.