Although immunotherapy appeared promising to treat mesothelioma during phase 2 trials, a randomized phase 3 trial showed results that researchers say are “disappointing.” With immunotherapy not offering the promise that mesothelioma patients hoped it did, patients are left with little hope for alternatives to beat this major killer.
Mesothelioma Treatment Methods
Mesothelioma is an aggressive form of cancer and difficult to treat. Researchers say that the median survival period is 12 to 20 months. Patients who have a nonepithelioid histologic subtype of tumor have a shorter expected lifespan.
Most patients are given a first line of treatment of platinum-based chemotherapy. However, there is not currently an effective standard second line of therapy for mesothelioma patients. Those who respond well to chemotherapy may be given another round of chemotherapy while others are given drugs that have a response rate of approximately 10%.
Due to the lack of a standard of care after the first round of chemotherapy, researchers have looked into alternatives such as immune checkpoint inhibitors.
Increase in Mesothelioma Cases
Every year, mesothelioma is diagnosed in more than 30,000 people and 25,000 people die from this fatal disease. Most cases are caused by exposure to asbestos fibers that cause inflammation in the cells of the lung until they eventually form cancer, often 20 to 50 years after this exposure. The worldwide number of deaths attributed to mesothelioma is expected to increase as individuals exposed to asbestos before it was banned continue to be diagnosed with the condition. Asbestos is not completely banned in the United States, so current exposure is still possible.
Many individuals who develop mesothelioma were exposed to asbestos in the workplace. However, people can also develop mesothelioma due to environmental exposure. Asbestos powder from closed plants pollutes the surrounding area, so residents may develop this deadly disease.
About the Treatment
Researchers provided patients with immunotherapy with pembrolizumab. Patients had malignant pleural mesothelioma that had progressed after first-line chemotherapy.
About the Study
Researchers from the PROMISE-meso study examined 144 patients with mesothelioma for a one-year period between 2017 and 2018. Most patients were approximately 70 years old and male. Approximately 90% of them had epithelioid tumors. Six months into the study, 25% of the patients who received pembrolizumab were progression free and 68.5% were still alive. In comparison, 27.4% of patients who received chemotherapy were progression free and 72.9% of this group were still alive.
Study Findings
Researchers were encouraged after phase II results showed nearly four times more patients were responding to immunotherapy than standard chemotherapy. However, the phase III trial showed patients did not significantly benefit from one treatment over another. Furthermore, patients with nonepithelioid tumors did better with chemotherapy than they did with immunotherapy.
Patients had a higher response rate with pembrolizumab than those treated with chemotherapy with numbers of 22% vs. 6%. However, this appeared to be due to patients who experienced a partial response. The duration of response was much shorter for those who used immunotherapy with 4.6 months vs. 11.2 months for patients who used chemotherapy.
Adverse effects of treatment were similar for immunotherapy and chemotherapy-treated patients with numbers of 69.4% and 72.9% overall, although the specific side effects were different. The overall response rates and disease control rates observed with pembrolizumab are comparable to previous results in phase 2 immunotherapy studies.
Ultimately, researchers concluded that immunotherapy offered no survival advantages over standard chemotherapy and a subset of patients could not be identified that would receive a long-term benefit by using immunotherapy. Even though more patients appeared to respond to immunotherapy, the responses did not delay progression or improve survival rates.
Because the results between immunotherapy and chemotherapy were similar, researchers suggest that immunotherapy could be used as an alternative to chemotherapy. It may also be possible to combine the treatments to see if this improves outcomes.
Results of Other Phase 2 Studies
Other phase 2 studies that have used pembrolizumab, avelumab and nivolumab have observed response rates between 20 and 30%. They have also observed disease control rates between 50 and 60%. Overall survival rates in these studies show 7 to 18 months. In comparison, the PROMISE-meso trial showed a survival rate with immunotherapy of 10.7 months.
