Straight Talk about Mesothelioma, a blog series created by Michael T. Milano, M.D., Ph.D., a radiation oncology specialist, as a resource for mesothelioma patients and their loved ones.
Scientists have seen new potential in an existing immunotherapy drug for mesothelioma. A breakthrough study on pembrolizumab, an antibody first approved to treat various cancers in 2014, has revealed that the drug could be pivotal in the treatment of mesothelioma. This drug helps stimulate the body’s immune system to fight cancer.
A rare and aggressive cancer caused by asbestos exposure that does irreversible damage to the lungs, pleural mesothelioma leaves patients with few options. Treatment methods, though varied, seldom succeed in improving prognosis. By the time of diagnosis, the disease is usually advanced well beyond a cure, and few patients live longer than a year.
Knowing this, would immunotherapy even be worth consideration? Would this treatment provide similar relief to others? Or have we finally found a drug that could make a difference?
Immunotherapy Makes ‘Encouraging’ Impact on Advanced Tumors
When a doctor recommends an initial treatment for cancer, they refer to this as first-line therapy. These are treatments proven in trials to work best for most patients–but sometimes they don’t. If and when the cancer grows while having received first-line therapy, a second-line therapy may be recommended. Unfortunately, with mesothelioma, treatment options are limited after first-line chemotherapy.
Researchers have been investigating potential second-line therapies for years, but pembrolizumab, a “checkpoint inhibitor,” is the first to show promising results.
“We’ve found this new class of drugs, checkpoint inhibitors, seems to be more effective than what’s been available in the past,” said Dr. Evan Alley, chief of hematology and medical oncology at the University of Pennsylvania, who led the research.
Alley’s team looked at data from an international clinical trial that began testing checkpoint inhibitors on patients with advanced mesothelioma tumors in 2014. The tumors were unresponsive to first-line treatment. However, results showed that 14 out of 25 patients taking pembrolizumab experienced tumor shrinkage. Moreover, the median time before the mesothelioma progressed was 6 months and the median overall survival was 18 months.
“Most patients who receive a second-line therapy have a life expectancy of about 6 or 7 months,” said Alley. “To have 4 patients still ongoing at 2 years is very encouraging.”
How Does Immunotherapy Work?
There are many different types of immunotherapy used and being investigated. Immune checkpoint inhibitors are, as their name suggests, drugs designed to assist the immune system.
This is necessary when cancer cells manipulate the body’s “checkpoints” to avoid attack from the immune system. To do this, they bind large amounts of a protein called PD-L1 to the checkpoint protein PD-1, which usually acts as an “off switch” to prevent immune cells (T cells) from attacking normal cells when fighting foreign ones. PD-L1 instructs T cells to leave the cancer cells alone. Pembrolizumab’s job is to block this binding protein, thereby boosting immune response.
Not only does the drug appear proficient in fighting mesothelioma cancer cells, but it also seems tolerable. Some trial participants experienced dry mouth, fatigue, nausea, and lack of appetite, but nothing serious enough to disqualify them from the study. In other studies (with different cancers) these drugs can cause debilitating or fatal auto-immune reactions, although this risk (which is low) is weighed against the benefit of these drugs controlling cancer for a longer duration than most chemotherapy drugs could.
This clinical trial for mesothelioma is ongoing, but more investigation is needed to confirm pembrolizumab’s capabilities as a second-line treatment. We don’t yet know if the drug holds more potential to shrink advanced tumors than chemotherapy.
“This study provides evidence that some patients can have long-term disease control with this drug, which we haven’t seen before,” Alley said, expressing near-future plans to begin testing pembrolizumab alongside other treatments. “We need to better understand what we can do next to make immunotherapy more effective for more patients.”