Access to Tyrosine Kinase Inhibitors and Survival in Patients with Advanced EGFR+ and ALK+ Positive Non–small-cell Lung Cancer Treated in the Real-World

Published:February 03, 2021DOI:


      • Oral drugs benefit patients with EGFR+ and ALK+ positive advanced lung cancer.
      • Approximately 18% of EGFR+ and ALK+ positive patients do not receive oral drugs.
      • Patients diagnosed in later years were less likely to receive oral drugs.
      • Underuse of EGFR and ALK oral drugs is associated with inferior survival.
      • Oncology providers need to identify and address access barriers to oral drugs.



      We assessed the proportion of patients with advanced epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) positive non–small-cell lung cancer (NSCLC) who receive tyrosine kinase inhibitors (TKIs) in the real-world, predictors of TKI use, and impact of TKI therapy on overall survival (OS).

      Materials and Methods

      We identified patients diagnosed with stage IV EGFR+ and ALK+ positive NSCLC from January 1, 2010 to December 31, 2018, in the Cancer Surveillance System registry and linked their records to Medicare and commercial insurance claims. We reported the proportions of patients with 1 or more TKI claims versus no TKI claims and used logistic regression to identify predictors of TKI use. We evaluated the effect of TKI use on OS by applying extended Cox proportional hazard models with TKI use as a time-dependent exposure and landmark analysis in a subcohort (N = 105). We adjusted Cox models for confounding patient characteristics.


      Of 117 eligible patients (median age = 69; 62% women; 88% EGFR+), 21 (17.9%) had no TKI claims. Diagnosis in 2015 to 2018 was independently associated with lower likelihood of TKI therapy compared with 2010 to 2014 (adjusted odds ratio, 0.29; P = .020). TKI use was associated with longer OS in a multivariate extended Cox model and in the landmark analysis (adjusted hazard ratio [HR], 0.58; 95% confidence interval [CI], 0.33; 0.99; P = .048; adjusted HR, 0.55; 95% CI, 0.30; 1.00; P = .050).


      Approximately 18% of patients with advanced EGFR+ and ALK+ positive NSCLC do not receive TKIs and have inferior survival. Further studies need to investigate barriers of access to TKIs in biomarker-selected patients.


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