Perspectives on the Treatment of Malignant Pleural Mesothelioma

Malignant mesothelioma is an aggressive tumor arising from the serosal outer linings of the lungs (pleurae), heart, abdomen, and testes. Treatment trials have focused on malignant pleural mesothelioma, which accounts for 90% of cases, is often diagnosed at an advanced stage, and invariably leads to death. Malignant pleural mesothelioma has proved to be a formidable challenge for clinicians and scientists, with the 5-year survival rate continuing to languish at 5 to 10%.1 By far the most important risk factor for the development of malignant mesothelioma is asbestos exposure, although other risk factors, including related minerals, are beginning to emerge.2 The United States and other Western countries are seeing a gentle decline in cases of malignant mesothelioma as a result of transforming work practices. In the United States, age-adjusted mortality has been reduced from almost 14 deaths per 1 million persons in 2000 to 11 deaths per 1 million in 2015.3 Britain (England, Scotland, and Wales) has one of the highest death rates in the world at 77 deaths per 1 million (from 2017 to 2019), although this rate is also in decline.4 However, regional successes in prevention through eliminating clinically significant exposure to asbestos have not been matched by the development of new treatments.

In this review, we reflect on the limited effect of the few positive phase 3 randomized, controlled studies, as well as recent trials examining the benefit of immunotherapy. We speculate about how rapid advances in our understanding of the genetics and biology of malignant pleural mesothelioma could translate into more effective therapies.