Previous studies have shown that the phosphatidylinositol 3-kinase (PI3K) pathway promotes tumor growth and drug resistance in NSCLC. Belgian authors Johan et al. reported a two-stage open phase II BASALT-1 (NCT01820325) study to investigate the safety and efficacy of the pan-PI3K inhibitor buparlisib (BKM120) in treating patients with PI3K pathway-activated relapsed NSCLC. (Journal of Thoracic Oncology, 2015, 10(9):1319C1327 The trial included patients with metastatic PI3K pathway-activated recurrent NSCLC (squamous lung cancer vs. non-squamous NSCLC) in phase I: both groups received buparlisib (100?mg/d) monotherapy based on 12-week PFS rates were analyzed independently for futility until the number of patients was less than 50%. Biomarkers were analyzed using archival tissue samples and circulating tumor DNA exploration. The study pre-screened 1242 patients, 13.5% of whom had PI3K pathway activation. As of June 5, 2014, two groups of patients (30 vs 33 patients) completed phase I treatment with 12-week PFS rates of 23.3% (95% CI 9.9C42.3) and 20.0% (95% CI 7.7C38.6), respectively, and phase II is not currently underway. PI3K pathway mutations in circulating tumor DNA were more consistent with metastatic mutations relative to primary site biopsies. The study concluded that despite pre-detection of PI3K genes to screen patients for treatment, phase 1 of the BASALT-1 study has not yet achieved its primary objective. PI3K inhibitors in combination with other drugs may be more effective than their monotherapy.