Research in context
Evidence before this study
We searched PubMed for reports published in English and Italian with the terms “mesothelioma”, “anti-CTLA4 antibody treatment”, and “immunotherapy in mesothelioma” from 2000, to 2014. Most of the reports identified were from the past 10 years. Patients with malignant mesothelioma progressing after first-line therapy have a high unmet medical need, in view of the absence of meaningful clinical effectiveness of existing salvage regimens. Anti-CTLA4 monoclonal antibody therapy has shown activity in several different types of tumour. CTLA4 blockade by tremelimumab (15 mg/kg every 90 days) provided initial signs of activity in patients with pretreated malignant mesothelioma; however, retrospective data from patients with melanoma suggested that this schedule could result in underexposure to tremelimumab. Therefore, we investigated an intensified schedule of tremelimumab (10 mg/kg once every 4 weeks for six doses, then every 12 weeks) in patients with advanced malignant mesothelioma.
Added value of this study
The clinical and immunological findings of this study provide evidence that this intensified schedule of tremelimumab seems to be active and safe in patients with previously treated malignant mesothelioma and suggest that it could eventually represent an effective second-line regimen for this group of patients with very poor prognosis.
Implications of all the available evidence
The same intensified schedule of tremelimumab is now being investigated in an ongoing randomised, double-blind, placebo-controlled, phase 2b study. Tremelimumab might also merit further exploration in malignant mesothelioma, both in the first-line setting and in combination or sequence with other immune checkpoint inhibitor monoclonal antibodies, such as those directed against programmed cell death protein-1 and its ligand, programmed death ligand-1.