Understanding the new therapeutic options for mesothelioma

• Published in: The lancet oncology 2021-10, Vol.22 (10), p.1353-1355
• Main Author: Kindler, Hedy Lee
• Format: Article
• Language: English
• Subjects: Bevacizumab; Carboplatin; Chemotherapy; Cisplatin; FDA approval; Gemcitabine; Immunotherapy; Mesothelioma; Monoclonal antibodies; Patients; Placebos; Platinum; Survival; Targeted cancer therapy; Tumors; Vascular endothelial growth factor receptors; Vinorelbine
• ISSN: 1470-2045; 1474-5488
• DOI: 10.1016/S1470-2045(21)00520-9

Since the US Food and Drug Administration (FDA) approved pemetrexed plus cisplatin for first-line treatment of mesothelioma in 2004,1 there has been a dearth of additional treatment options for this disease. Despite substantial effort, no other phase 3 study achieved a positive outcome for another 12 years, until the MAPS trial showed that the addition of bevacizumab to pemetrexed plus platinum improved progression-free and overall survival.2 Although it is not approved by regulatory agencies, bevacizumab is endorsed in treatment guidelines for patients with no contraindications to its use,3 with variable uptake depending on the geographical region. CheckMate 743 changed the first-line standard of care from pemetrexed plus platinum to ipilimumab plus nivolumab.5 Although overall survival was superior for the immunotherapy doublet compared with chemotherapy across all histological subtypes (18·1 vs 14·1 months respectively), the survival benefit was most dramatic for patients with non-epitheloid tumours, in whom survival more than doubled, from 8·8 months with chemotherapy to 18·1 months with immunotherapy.5 CONFIRM showed that single-agent nivolumab improved progression-free and overall survival compared with placebo in previously treated patients.6 NVALT19 suggested that switch-maintenance gemcitabine after pemetrexed plus platinum could improve progression-free survival, but not overall survival, compared with best supportive care.7 VIM reported that oral vinorelbine achieved superior progression-free and overall survival compared with placebo in previously treated patients.8 In The Lancet Oncology, Carmine Pinto and colleagues report the RAMES trial,9 a multicentre, placebo-controlled, randomised, phase 2 trial of gemcitabine with or without the VEGFR-2 antibody ramucirumab in patients with malignant pleural mesothelioma who progressed after first-line treatment with pemetrexed plus cisplatin or carboplatin.