Comprehensive screening of target molecules by next-generation sequencing in patients with malignant solid tumors: guiding entry into phase I clinical trials

It is still controversial whether comprehensive genome screening of target molecules by next generation sequencing (NGS) is needed to increase clinical efficacy of investigational drugs or accelerate drug development, although several studies are being carried out. Therefore, we performed a prospective study to evaluate the feasibility of comprehensive gene screening in this setting. Our findings indicate that actionable alterations were identified in 45% of the analyzed patients, most frequently in those with breast cancer. Common actionable alterations were found in PIK3CA mutation, BRCA2 mutation, ERBB2 amplification, and CCND1 amplification. In total, 22% of the analyzed patients could be entered into phase I clinical trials, and 8% of them were treated with “matched” drugs. Among patients who received matched therapies, response and disease control rates were 33 and 78%, respectively. On the other hand, in the patients who received “non-matched” therapy, the objective response rate was 6%. We believe this data indicates that NGS-based molecular pre-screening is a potent platform for use before patient entry into phase I trials. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12943-016-0553-z) contains supplementary material, which is available to authorized users.