Abstract
Malignant pleural mesothelioma (MPM) is an aggressive cancer characterised by modest sensitivity to systemic chemotherapy. The standard treatment remains platinum-based chemotherapy with pemetrexed. Recently, the addition of an antiangiogenic drug, bevacizumab, to first-line chemotherapy has been shown to improve overall survival. All the patients, unfortunately, will progress, and currently, there is no standard treatment approved in second-line. Recently, the results of the NGR015 phase III randomised with NGR-hTNF plus chemotherapy versus placebo in addition to physician’s choice second-line chemotherapy for MPM have been published. Despite encouraging data achieved in previous phase I and phase II studies, the NGR-hTNF drug failed to meet the primary endpoint of the study, although a signal of activity was observed in the group of patients who had a shorter treatment failure interval from the first-line treatment.Hereby, we start from this recent trial to highlight once more the importance of thoroughly investigating possible predictive factors during the early drug development phase to allow more efficient phase III trial design, thus avoiding the possibility of potentially effective molecules like NGR-hTNF, continuing to be wasted.
Highlights
Malignant pleural mesothelioma (MPM) is an aggressive cancer characterised by modest sensitivity to systemic chemotherapy [1]
The results of the NGR015 [2] phase III randomised with NGR-hTNF, a new drug which increases the intratumoural chemotherapy penetration and promotes the T cell infiltration by modifying the tumour microenvironment, versus placebo in addition to physician’s choice second-line chemotherapy for MPM have been reported
It is not the first time that treatment-free interval (TFI) has been shown to be predictive of better outcome in patients treated with antiangiogenic drugs in the second-line setting, as for example in non-small cell lung cancer (NSCLC) within the LUME-Lung trial by the addition of nintedanib to docetaxel [3]
Summary
The addition of an antiangiogenic drug, bevacizumab, to first-line chemotherapy has been shown to improve overall survival (OS) in a large phase III trial from 16.1 months up to 18.8 months. Well-designed clinical trials in the second-line setting are essential to meet this need. The study didn’t meet its primary endpoint OS in the intention to treat the population, but it suggested a possible clinically meaningful interaction in the subgroup of patients with a short treatment-free interval (TFI) from the first-line therapy, considering as its cutoff the median time observed in the post-hoc exploratory sensitivity analysis.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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 callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
