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

Ahmed Mohieldin,1,2 Ayman Rasmy,1,3,4 Mohamed Ashour,2,5 Muath Al-Nassar,6 Rola H Ali,7,8 Fahad G El-Enezi6 1Medical Oncology, Zagazig University Hospitals, Zagazig, Egypt; 2Medical Oncology Department, Sheikha Badriya Alsabah Centre, Kuwait Cancer Control Center, Shuwaikh, Kuwait; 3Medical Oncology Department, King Saud Medical City, Riyadh, Saudi Arabia; 4Medical Oncology Department, King Fahad Specialist Hospital, Dammam, Saudi Arabia; 5Clinical Oncology, Al-Azhar University, Cairo, Egypt; 6Thoracic Oncology – Sheikha Badriya Alsabah Centre, Kuwait Cancer Control Center, Shuwaikh, Kuwait; 7Department of Pathology, Faculty of Medicine, Kuwait University, Safat, Kuwait; 8Molecular Laboratory, Kuwait Cancer Control Center, Shuwaikh, Kuwait 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: non-small-cell lung cancer, anaplastic lymphoma kinase gene, crizotinib, overall survival, progression-free surviva