Pazopanib in Molecularly Selected Patients With Advanced NSCLC

There has been a limited benefit from anti-angiogenesis drugs in patients with NSCLC. Bevacizumab provides a modest survival improvement when added to chemotherapy and VEGFR tyrosine kinase inhibitors have been associated with minimal efficacy as single agents and increased toxicity when combined with chemotherapy. We postulate that the response rates and survival may be improved with a better selection of patients based on abnormalities of the targets for the drugs. According to the preliminary data from the cancer genome atlas (TCGA), the targets of pazopanib are altered in 28% of patients with adenocarcinoma and 24% of patients with squamous cell lung cancer. Since, despite the molecular selection prior to treatment, only a small percentage of patients will benefit from the treatment, we plan to further investigate those patients with whole exome sequencing in both the pre-treatment samples to identify the predictors for response and at the time of progression, with repeated biopsy, in an attempt to identify the predictors for secondary resistance. By identifying more reliable predictors for response to pazopanib, our study may help to establish its role in the treatment of NSCLC.