Fennell DA, et al. - Based on the finding that inhibition of focal adhesion kinase selectively kills mesothelioma cells that express low levels of moesin-ezrin-radixin-like protein (merlin), researchers performed this global, double-blind, randomized, placebo-controlled trial to determine the impact of defactinib on progression-free survival (PFS) in patients with malignant pleural mesothelioma (MPM), when used as maintenance therapy following standard first-line chemotherapy. Participants had advanced MPM and controlled disease following at least four cycles of first-line chemotherapy. Following stratification for merlin, 344 patients randomly received (in a 1:1 fashion) either oral defactinib (n = 173) or placebo (n = 171) until disease progression, unacceptable toxicity, or withdrawal occurred. For defactinib vs placebo, the median PFS of 4.1 months vs 4.0 months and median overall survival (OS) of 12.7 months vs 13.6 months was reported. Nausea, diarrhea, fatigue, dyspnea, and decreased appetite were most commonly experienced as grade 3 or worse adverse events. Overall, defactinib after first-line chemotherapy in patients with merlin-low MPM did not result in improved PFS and OS and therefore, cannot be recommended as maintenance therapy for advanced MPM.