Timeliness of EGFR/ALK Inhibitor Treatment and Survival in Lung Cancer: A Population-Based Analysis

Clin Lung Cancer. 2024 Nov;25(7):e304-e311. doi: 10.1016/j.cllc.2024.04.019. Epub 2024 Apr 30.

Abstract

Background: ALK or EGFR inhibitor is an ideal frontline treatment for patients with advanced non-small cell lung cancer (NSCLC) harboring targetable alteration in ALK or EGFR. However, in the real-world setting, frontline treatment may be delayed or not ideal. For such patients, the benefit of initiating ALK or EGFR inhibitor at a later timepoint remains uninvestigated.

Methods: We utilized a nationwide electronic health record-derived, deidentified database collected from diverse oncology practices across the United States to investigate the timeliness of preferred targeted therapy (PTT). Individualized data obtained from patients with stage IV NSCLC at diagnosis treated with PTT from 2018 to 2023 were analyzed.

Results: Data from 3250 patients were analyzed: 2640 patients (81%) with EGFR mutation and 610 patients (19%) with ALK rearrangement. The median time to PTT was 7 weeks from diagnosis with 26.4% of patients started PTT within 1 month. Landmark analyses using timepoints ranging from 1 to 12 months after diagnosis showed that at all timepoints, patients who had started on PTT had a significantly better survival than those who had not. In a multivariable analysis, time to PTT ≤ 1 month from diagnosis was an independent predictor of survival: HR 0.74 (95% CI: 0.62-0.89), P = .002. Time to PTT was significantly associated with age, smoking status and genomic class.

Conclusions: In this population-based analysis, an initiation of PTT occurring as late as at least 1 year from diagnosis still resulted in a significant survival benefit, though the magnitude of benefit appeared decreased as time passed.

Keywords: Molecular testing; Non-small cell; Physician practice; Real-world data; Targeted therapy; Tyrosine kinase inhibitor.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anaplastic Lymphoma Kinase* / antagonists & inhibitors
  • Anaplastic Lymphoma Kinase* / genetics
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / mortality
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • ErbB Receptors* / antagonists & inhibitors
  • ErbB Receptors* / genetics
  • Female
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / mortality
  • Lung Neoplasms* / pathology
  • Male
  • Middle Aged
  • Molecular Targeted Therapy / methods
  • Mutation
  • Protein Kinase Inhibitors* / therapeutic use
  • Retrospective Studies
  • Survival Rate
  • Time-to-Treatment
  • United States / epidemiology

Substances

  • ErbB Receptors
  • Anaplastic Lymphoma Kinase
  • Protein Kinase Inhibitors
  • EGFR protein, human
  • ALK protein, human