Combination Strategies Using EGFR-TKi in NSCLC Therapy: Learning from the Gap between Pre-Clinical Results and Clinical Outcomes.

Although epidermal growth factor receptor (EGFR) inhibitors have been used to treat non-small cell lung cancer (NSCLC) for decades with great success in patients with EGFR mutations, acquired resistance inevitably occurs after long-term exposure. More recently, combination therapy has emerged as a promising strategy to overcome this issue. Several experiments have been carried out to evaluate the synergism of combination therapy both in vitro and in vivo . Additionally, many clinical studies have been carried out to investigate the feasibility of treatment with EGFR-tyrosine kinase inhibitors (TKi) combined with other NSCLC treatments, including radiotherapy, cytotoxic chemotherapies, targeted therapies, and emerging immunotherapies. However, a significant gap still exists when applying pre-clinical results to clinical scenarios, which hinders the development and use of these strategies. This article is a literature review analysing the rationalities and controversies in the transition from pre-clinical investigation to clinical practice associated with various combination strategies. It also highlights clues and challenges regarding future combination therapeutic options in NSCLC treatment.