Abstract
BackgroundMesothelioma is an incurable, apoptosis-resistant cancer caused in most cases by previous exposure to asbestos and is increasing in incidence. It represents a growing health burden but remains under-researched, with limited treatment options. Early promising signals of activity relating to both PD-L1- and PD-1-targeted treatment in mesothelioma implicate a dependency of mesothelioma on this immune checkpoint. There is a need to evaluate checkpoint inhibitors in patients with relapsed mesothelioma where treatment options are limited.MethodsThe addition of 12 months of nivolumab (anti-PD1 antibody) to standard practice will be conducted in the UK using a randomised, placebo-controlled phase III trial (the Cancer Research UK CONFIRM trial). A total of 336 patients with pleural or peritoneal mesothelioma who have received at least two prior lines of therapy will be recruited from UK secondary care sites. Patients will be randomised 2:1 (nivolumab:placebo), stratified according to epithelioid/non-epithelioid, to receive either 240 mg nivolumab monotherapy or saline placebo as a 30-min intravenous infusion. Treatment will be for up to 12 months. We will determine whether the use of nivolumab increases overall survival (the primary efficacy endpoint). Secondary endpoints will include progression-free survival, objective response rate, toxicity, quality of life and cost-effectiveness. Analysis will be performed according to the intention-to-treat principle using a Cox regression analysis for the primary endpoint (and for other time-to-event endpoints).DiscussionThe outcome of this trial will provide evidence of the potential benefit of the use of nivolumab in the treatment of relapsed mesothelioma. If found to be clinically effective, safe and cost-effective it is likely to become the new standard of care in the UK.Trial registrationEudraCT Number: 2016–003111-35 (entered on 21 July 2016); ClinicalTrials.gov, ID: NCT03063450. Registered on 24 February 2017.
Highlights
Mesothelioma is an incurable, apoptosis-resistant cancer caused in most cases by previous exposure to asbestos and is increasing in incidence
Promising signals of activity relating to both PD-L1- and PD-1targeted treatment in mesothelioma implicate a dependency of mesothelioma on this immune checkpoint, and support the development of a randomised phase III trial to evaluate the efficacy of nivolumab
Programmed cell death 1 (PD-1) checkpoint inhibition has revolutionised the treatment of melanoma and is expected to become standard of care in NSCLC
Summary
Mesothelioma is an incurable, apoptosis-resistant cancer caused in most cases by previous exposure to asbestos and is increasing in incidence It represents a growing health burden but remains under-researched, with limited treatment options. Chemotherapy is currently the standard of care in the first-line setting in which two positive, randomised phase III trials have been reported, showing improved survival with the addition of pemetrexed or raltitrexed to cisplatin, respectively [3, 4]. Vinorelbine is used in some centres, as phase II trials have shown this drug to have promising activity in the second-line treatment of mesothelioma. Due to the availability of second-line options, either within the VIM trial or off study, the CONFIRM trial aims to evaluate immunotherapy in the third-line setting, a clinical situation in which current standard of care is active symptom control only. Best supportive care has been chosen as the comparator arm in this study
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
