[Malignant pleural mesothelioma: rare and aggressive but with new therapeutic perspectives]

Malignant pleural mesothelioma: rare and aggressive but with new therapeutic perspectives. CMalignant pleural mesothelioma (MPM) is a rare tumour secondary to occupational asbestosis exposure. Its incidence has increased continuously since last thirty years, but has reached a plateau in France in men, earlier than anticipated. MPM incidence reaches 100 cases/million/year in an occupationally exposed population versus less than 1 case/million/year in general population, leading to 800 to 1000 new cases, yearly, in France. Molecular carcinogenesis of MPM is incompletely understood, but involves NF2, WT1 RASSF1, p16 gene alterations and the more recently described BAP-1. These genes are involved in apoptosis control, cell invasion and motility, cell division, and DNA repair control. Diagnosis relies on thoracoscopy and large pleural biopsies. Histological diagnosis remains an actual dilemma, relying on immunohistochemical analysis as described by the French MESOPATH group. Therapeutic strategy includes precocious tracts irradiation following drainage or thoracoscopy, to prevent permeation nodules. In selected patients, debulking surgery (pleurectomy-decortication) can still be discussed. First-line chemotherapy is based on a doublet of pémétrexed and cisplatin, for ten years, that demonstrated overall survival and quality of life improvement in a seminal phase 3 trial. As mesothelioma cells are known to secrete high amounts of VEGF, the monoclonal antibody targeting VEGF, bevacizumab (Avastin), in association with pemetrexed- cisplatin has been shown, in 448 patients, to improve overall survival (to nearly 19 months), and progression-free survival in the randomized phase 3 trial, Mesothelioma Avastin Pemetrexed Study (MAPS), sponsored by the French Intergroup (IFCT). Immune check-point inhibitors are currently tested in phase 2 trials and could then represent the future major therapeutic improvement in these patients.