Efficacy and safety of crizotinib in patients with anaplastic lymphoma kinase-positive advanced-stage non-small-cell lung cancer

Abstract

Introduction: Lung cancer is the leading cause of cancer mortality worldwide, despite advances in management, especially with targeted agents and immunotherapy. Numerous oncogenes have been identified that control the growth of these malignancies. Anaplastic lymphoma kinase (ALK) is a tyrosine kinase that develops distorted functioning as a result of chromosomal rearrangement. Crizotinib, a tyrosine kinase inhibitor (TKI), was approved by the Food and Drug Administration (FDA) in 2011 for the treatment of advanced ALK-positive non-small-cell lung cancer (NSCLC).

Patients and methods: In this chart review, we compiled data from two cancer hospitals in Kuwait and Saudi Arabia which were collected from patients with advanced NSCLC treated between January 2013 and September 2017 with crizotinib after diagnosed with ALK-positive disease. Crizotinib 250 mg BID was given orally with/without food intake. We assessed overall survival (OS), objective response rate (ORR), progression-free survival (PFS), duration of the response, and dose reduction/cessation.

Results: De-identified data from 38 subjects were compiled. Their median age was 53 years, 65.8% were male, the 1-year OS was 88%, and the PFS was 16.5 months. Two cases (5.3%) had a complete response (CR), while 17 (44.7%) had a partial response (PR). Side effects of grade III/IV occurred, including elevated transaminase levels, diarrhea, and prolonged QT intervals, in 8% patients, with dose reduction in six patients (15.8%).

Conclusion: In NSCLC, crizotinib is a viable treatment option with good response and tolerable toxicity for patients with ALK-positive advanced disease.

Keywords: anaplastic lymphoma kinase gene; crizotinib; non-small-cell lung cancer; overall survival; progression-free survival.

Figure 1

Kaplan–Meier estimates of survival functions in intention-to-treat population. Notes: (A) The mean PFS was 17.678±4.227 months (range: 9.393–25.963). (B) The 1-year survival was 88.6% and 5-year survival as 34.8%.The mean OS was 50.097±6.547 months (rang: 37.265–62.928). Abbreviations: OS, overall survival; PFS, progression-free survival.

Figure 2

Kaplan–Meier estimates of survival functions stratified by prior platinum-based chemotherapy in intention-to-treat population. Notes: (A) Patients with first line crizotinib had less mean PFS of 14.834±6.789 months (range: 1.527–28.141) and patients received crizotinib as subsequent lines with PFS of 20.928±4.958 months with no statistically significant outcome (P=0.487). (B) Patients with first line crizotinib had longer mean OS of 48.794±8.941months and patients received crizotinib as subsequent lines with OS of 46.790±7.827 months with no statistically significant outcome (P=0.456). Abbreviations: OS, overall survival; PFS, progression-free survival.