In the PROMISE-meso trial, scientists compared the efficacy of immunotherapy with pembrolizumab, a checkpoint inhibitor, against standard chemotherapy. They did this in mesothelioma patients who had relapsed after receiving first-line treatment. Their findings showed that these patients responded to immunotherapy, almost four times more.
Sadly, the observed greater responses failed to lead to a delay in the progression of the disorder or improved survival chances.
“These findings are disappointing but, as in previous studies, some patients benefitted from immunotherapy for long periods,” said study author Dr. Sanjay Popat, of Royal Marsden Hospital NHS Foundation Trust in London, UK. “If we can find out how this happens, we will have a better idea of which patients should preferentially receive this treatment over chemotherapy.”
In spite of the mediocre results, Popat said that immunotherapy showed enough potential to serve as an alternative to chemotherapy.
Results from the PROMISE-meso trial were presented at the 2019 edition of the European Society of Medical Oncology (ESMO) annual meeting.
Incidence of mesothelioma and associated deaths
Mesothelioma is not one of the most common forms of cancer, but it ranks among the most fatal.
An estimate has it that there are more than 30,000 diagnoses in a year on average. More than 25,000 people die as a result of the disorder annually.
Patients typically die within two years of being diagnosed with mesothelioma.
Exposure to asbestos fibers contributes hugely to the incidence of this cancer form. Researchers say this is responsible for more than 80 percent of cases.
Mesothelioma does not develop immediately after asbestos exposure. Inflammation of the mesothelial cells in the lung occurs at the initial stage. It usually takes decades before cells turn cancerous.
There has been a reduction in the incidence of this condition in the USA, Australia, and Western Europe. This decline is a result of strict regulations in these places, as regards asbestos.
The incidence of asbestos deaths has dropped gradually over the years in America. Death rates are somewhat stable in Western Europe.
Later bans on asbestos in other countries have kept death rates high in many of them. Mortality due to mesothelioma is still rising in Japan and Eastern Europe.
Dr. Federica Grosso of the Mesothelioma and Rare Cancers Unit of Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo in Alessandria, Italy said that new cases and deaths were common in some “hotspots” in the country. She stated that the incidence of mesothelioma in one of these places, Casale Monferrato, is more than 20 times higher than in other parts of Italy.
Casale Monferrato had the world’s largest asbestos plant before it was shut down in 1987.
“The worldwide number of deaths is expected to rise as people exposed to asbestos before it was banned continue to be diagnosed many years later,” Grosso said.
She stated that there is a partial or full asbestos ban in only 66 countries across the globe. The bulk of the current production takes place in middle and lower-income countries.
Immunotherapy as an alternative treatment
Patients have very limited options currently for treating mesothelioma. In fact, a combination of pemetrexed and platinum derivatives is the only approved treatment regimen.
No effective, standard second-line treatment is available at the moment for people with this disorder. A patient may only receive another course of the approved regimen or other medications, such as gemcitabine (Gemzar) or vinorelbine (Navelbine).
The research team studied 144 patients who had advanced pre-treated cases of mesothelioma in Phase 3 PROMISE-meso trial. These individuals were randomly selected to receive 200mg of pembrolizumab once every three weeks or standard chemotherapy featuring gemcitabine and vinorelbine.
For pembrolizumab, the median overall survival was 10.7 months. This compared fairly well with 11.7 months reported for chemotherapy.
The group that received immunotherapy also showed slightly fewer adverse events. There was one fatality in each of the groups.
The hope is that these findings may lead to a new treatment. The results stress the need to investigate why immunotherapy seems to produce a response in some patients and not in others.
“Although we did not see better survival with immunotherapy in the PROMISE-meso study, the responses are encouraging and the results of the ongoing trials of checkpoint inhibitor treatment in earlier stage mesothelioma will be very important to clinicians,” said Grosso, who emphasized the need for better first and second-line treatments for this thoracic cancer form.