Switch Maintenance Gemcitabine after First Line Chemotherapy in Patients with Malignant Mesothelioma: A Randomized Open Label Phase II Trial (NVALT19)

Background: All patients with malignant mesothelioma develop progressive disease after first line therapy. Some studies have addressed maintenance therapy, none showed a great impact. Gemcitabine, an active drug in mesothelioma, was tested in the NVALT19 study in a switch maintenance setting. Methods: This open label randomized phase II study in 18 Dutch hospitals, recruited patients with unresectable mesothelioma who did not progress after first line chemotherapy (platinum-pemetrexed), World Health Organization performance status ≤ 2 and an adequate organ function. Key exclusion criteria were seriously disabling conditions or symptomatic central nervous system metastases. Patient were 1:1 randomised to maintenance gemcitabine (1250 mg/m2, intravenous, day 1 and 8, 3 weeks schema) or best supportive care (BSC,) using minimisation method. Primary endpoint was progression-free survival (PFS) in the intention-to-treat population. Safety was analysed in all participants who received one dose of study drug. Findings: From March 20, 2014, to February 27, 2019, 130 patient were randomized (65 to gemcitabine and 65 to BSC). PFS was significant longer with gemcitabine (median 6.2) than with BSC (3·2 months; hazard ratio (HR) 0·46; 95% confidence interval [CI], 0·31 to 0·68; p