Real-world anaplastic lymphoma kinase (ALK) rearrangement testing patterns, treatment sequences, and survival of ALK inhibitor-treated patients

Curr Med Res Opin. 2019 Mar;35(3):535-542. doi: 10.1080/03007995.2018.1533458. Epub 2018 Nov 9.

Abstract

Background: The anaplastic lymphoma kinase (ALK) treatment landscape is crowded following recent ALK inhibitor approvals, and updated information on real-world treatment patterns in advanced non-small-cell lung cancer (aNSCLC) with ALK rearrangement (ALK+) is needed.

Methods: This retrospective US cohort study used Flatiron Health's longitudinal electronic health record (EHR)-derived database. Patients (≥ 18 years old) diagnosed with stage IIIB/IV aNSCLC, with documented ALK rearrangement and ≥2 visits after January 1, 2011 were followed until February 28, 2016. Patients enrolled on a clinical trial or exposed to ALK inhibitors other than crizotinib or ceritinib were excluded. Treatment patterns, time and type of biomarker testing, and overall survival (OS) were analyzed.

Results: Median age (n = 300) was 62.5 years; 55% female; 48% non-smokers; 8.7% central nervous system (CNS) metastases at diagnosis. Overall, 73% and 86% received their first ALK biomarker test before/at diagnosis, or before/during first-line treatment, respectively. In total, 90.0%, 78.1%, and 74.7% received first-, second-, and third-line therapy, respectively. Most patients received ALK-targeted treatment; 62% received crizotinib, of which 21% reported a dose reduction. Progression was the most common reason for crizotinib (78%) and ceritinib (41%) discontinuation. Median OS was 29.4 months (95% CI =24.7-39.6) overall; 27.1 months (95% CI =22.0-35.0) in patients with CNS metastases, and 36.9 months (95% CI =25.1-not reached) without.

Conclusions: Despite widespread crizotinib use in patients with ALK+ aNSCLC, a high proportion of patients progressed. Ongoing analyses of EHR-derived cohorts are valuable in assessing real-world testing rates and therapeutic use of ALK inhibitors.

Keywords: positive; Flatiron; NSCLC; Real-world data; Treatment sequence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • 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
  • Female
  • Gene Rearrangement*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Protein Kinase Inhibitors / therapeutic use*
  • Retrospective Studies

Substances

  • Protein Kinase Inhibitors
  • ALK protein, human
  • Anaplastic Lymphoma Kinase