Parameters for individualizing systemic therapy in non-small cell lung cancer

Rational drug design based on molecular targets is starting to revolutionize cancer care. To maximize its potential for patients, a concomitant leveraging of molecular knowledge for selection of patients to future and current therapeutic options is paramount. The terms “individualized”, “personalized”, or “precision therapy” are currently used to describe these efforts. Here, we summarize current knowledge for selection of systemic targeted and cytotoxic therapy for patients with non-small-cell lung cancer. Based on this knowledge, we present a potential decision algorithm to best select patients for currently available therapies, which include the treatment options single-agent erlotinib or gefitinib, the ALK inhibitor crizotinib, double agent gemcitabine and platinum, double agent platinum and pemetrexed, and as a default option a taxane combined with a non-platinum drug, for instance a vinca alkaloid. The addition of bevacizumab to double-agent chemotherapy is also discussed. Currently available data on predictive biomarkers are largely based on subgroup or companion biomarker analyses of patient cohorts or clinical trials. Current and emerging markers must be incorporated prospectively into the design of clinical trials that test novel and established agents to better understand their clinical utility and to refine selection parameters and marker interactions. Future development will lead to increasing complexity in clinical decision making with substantial anticipated benefits to patients including increased therapeutic efficacy, reduced toxicity, and better quality of life.