Strategies to Improve Outcomes of Patients with EGFR-Mutant Non–Small Cell Lung Cancer: Review of the Literature

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Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) monotherapy has been regarded as the standard first-line treatment of advanced non–small cell lung cancer (NSCLC) in patients with sensitive epidermal growth factor receptor gene (EGFR) mutations. Acquired resistance is inevitable, however, which presents a challenge in the management of patients with such mutations. Here, we summarize the clinical evidence on treatment strategies for both EGFR TKI–naive and acquired EGFR TKI–resistant NSCLC. We reviewed the published literature and abstracts of oral and poster presentations from international conferences addressing treatment strategies that are in use or in clinical development to improve the survival of patients who are EGFR TKI naive and EGFR TKI resistant. Various strategies have been explored to manage EGFR TKI resistance with the aim of prolonging the survival of patients with EGFR-mutant NSCLC. Combination strategies in the first-line treatment have been studied most to improve the benefit from EGFR TKI monotherapy and delay the occurrence of resistance. After failure of EGFR TKI monotherapy, continuation of EGFR TKI therapy combined with chemotherapy, immunotherapy, or targeted agents has been used to overcome the development of resistance. In addition, novel compounds designed to act on specific targets associated with EGFR TKI resistance have been in continued clinical development. Treatment regimens that are superior to EGFR TKI monotherapy in the first-line or to overcome acquired EGFR TKI resistance in patients with NSCLC and EGFR mutations still need to be developed. Results of ongoing studies will provide more insight into effective treatment strategies for patients with EGFR mutations.