Experience of using сrizotinib in patients with ALKpositive non-small cell lung cancer

Abstract

Introduction. Sufficient experience has been gained with the use of target drugs in patients with ALK-positive non-small cell lung cancer (NSCLC) over the past years. The multikinase inhibitor crizotinib was the first drug approved for use. The drug passed the accelerated registration in the United States, showing an indisputable advantage over standard chemotherapy both in untreated patients and patients, who had previously received cytostatic therapy. Brain metastasis is the manifestation of acquired resistance to crizotinib in almost half of patients, which requires local monitoring and/or prescription of the nextgeneration ALK inhibitors – ceritinib or alectinib. Experience has proven that it is sequential targeted therapy with the nextgeneration ALK inhibitors with a wider spectrum of anti-tumour activity and penetrating the blood-brain barrier that significantly improves the overall survival of these patients after disease progression on crizotinib. It appears then that the second generation drugs – ceritinib and particularly alectinib – show more impressive results when they are prescribed in the firstline therapy and have now replaced crisotinib in the clinical guidelines. Crizotinib has long remained the only target drug to treat ALK-positive patients in the Russian Federation. Material and methods. In our work, we analysed the crizotinib therapy outcomes in 104 patients with translocation in the ALK gene. The drug was prescribed in a standard dose of 250 mg orally twice per day. Treatment continued until disease progression or intolerable toxicity. Results. The objective response was 56.8%. The median time to progression was 13 months; the median overall survival was 46 months. Conclusion. The obtained data are consistent with previously published data and confirm the effectiveness of the drug in comparison with the previously available universal standard – combination chemotherapy.

Keywords

• alk translocation
• non-small cell lung cancer
• targeted therapy
• crizotinib