Switch-Maintenance Gemcitabine After First-Line Chemotherapy In Patients With Malignant Pleural Mesothelioma

Malignant pleural mesothelioma is a rare but aggressive cancer of the pleural lining.Malignant pleural mesothelioma accounted for 30,870 new cancer cases and 26,278 deathsworldwide in 2020.In Egypt, Malignant pleural mesothelioma accounted for 337 new cases and 307 deaths in2020.Long‐term exposure to asbestos is a well‐established risk factor for Malignant pleuralmesothelioma. It accounts for almost 80% of cases.Malignant pleural mesothelioma is classified into three histologic subtypes: epithelioid,sarcomatoid, and biphasic. Epithelioid histology confers the most favorable prognosis andsarcomatoid the least.The majority of patients with Malignant pleural mesothelioma present with breathlessness,chest pain or both. Other symptoms include fatigue, anorexia, weight loss, sweats andmalaise.Radiological imaging should be undertaken in all patients as it can provide valuablediagnostic and staging information. Further investigation of suspected Malignant pleuralmesothelioma requires sampling of pleural fluid for biochemical and cytologicalexamination. Biopsies are usually required to confirm the diagnosis and identify thehistological sub‐type.Patients with Malignant pleural mesothelioma should be managed by an experiencedmultidisciplinary team. Treatment options include surgery, radiation therapy andchemotherapy.Front line polychemotherapy is considered the standard of care, whereas single agentchemotherapy has shown limited efficacy with disappointing response rates.A pivotal trial led to the establishment of Cisplatin and Pemetrexed as standard firstline regimen for unresectable Malignant pleural mesothelioma.A recent phase II trial from Cancer and Leukemia Group B showed that maintenancePemetrexed after 4 to 6 cycles of doublet chemotherapy induction did not prolongprogression free survival over placebo.Adding Bevacizumab to first line platinum doublet resulted in an overall survival andprogression free survival gain in the phase III French trial MAPS .Bevacizumab wascontinued as maintenance every three weeks following completion of six cycles ofchemotherapy.In a phase III trial NVALT 5 , Thalidomide versus active supportive care for maintenancein patients with malignant mesothelioma after first‐line chemotherapy showed no benefitin time to progression.First line Nivolumab plus Ipilimumab in phase III trial checkmate 743 providedsignificant and clinically meaningful improvements in overall survival versus standard ofcare chemotherapy.Unfortunately, nearly all patients progress during or after first‐line therapy, and nostandard second line recommended treatments exist after platinum based regimen.Retreatment with pemetrexed, eventually associated with platinum compound, may be offeredin patients who achieved durable disease control more than 6 months with first linechemotherapy.Single agent chemotherapy with Vinorelbine or Gemcitabine is the preferred choice assecond line treatment , mainly based on retrospective analyses or small phase II trials.