Perioperative Treatment Strategies in EGFR-Mutant Early-Stage NSCLC: Current Evidence and Future Challenges

J Thorac Oncol. 2024 Feb;19(2):199-215. doi: 10.1016/j.jtho.2023.09.1451. Epub 2023 Sep 30.

Abstract

Treatment with 3 years of adjuvant osimertinib is considered a new standard in patients with completely resected stage I to IIIA NSCLC harboring a common sensitizing EGFR mutation. This therapeutic approach significantly prolonged the disease-free survival and the overall survival versus placebo and revealed a significant role in preventing the occurrence of brain metastases. However, many unanswered questions remain, including the optimal duration of this therapy, whether all patients benefit from adjuvant osimertinib, and the role of adjuvant chemotherapy in this population. Indeed, there is a renewed interest in neoadjuvant strategies with targeted therapies in resectable NSCLC harboring oncogenic drivers. In light of these considerations, we discuss the past and current treatment options, and the clinical challenges that should be addressed to optimize the treatment outcomes in this patient population.

Keywords: Adjuvant osimertinib; EGFR-mutant; Early-stage NSCLC; Minimal residual disease.

Publication types

  • Review

MeSH terms

  • Acrylamides*
  • Aniline Compounds*
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / surgery
  • ErbB Receptors / genetics
  • ErbB Receptors / therapeutic use
  • Humans
  • Indoles*
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / surgery
  • Mutation
  • Neoplasm Staging
  • Protein Kinase Inhibitors / adverse effects
  • Pyrimidines*

Substances

  • osimertinib
  • Protein Kinase Inhibitors
  • ErbB Receptors
  • EGFR protein, human
  • Acrylamides
  • Aniline Compounds
  • Indoles
  • Pyrimidines