Sequential Therapy with Crizotinib and Alectinib in ALK-Rearranged Non–Small Cell Lung Cancer—A Multicenter Retrospective Study

• Published in: Journal of thoracic oncology Vol. 12; no. 2; pp. 390 - 396
• Main Authors: Ito, Kentaro, Hataji, Osamu, Kobayashi, Hiroyasu, Fujiwara, Atsushi, Yoshida, Masamichi, D’Alessandro-Gabazza, Corina N, Itani, Hidetoshi, Tanigawa, Motoaki, Ikeda, Takuya, Fujiwara, Kentaro, Fujimoto, Hajime, Kobayashi, Tetsu, Gabazza, Esteban C., Taguchi, Osamu, Yamamoto, Nobuyuki
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2017; Copyright by the International Association for the Study of Lung Cancer
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - genetics; Adenocarcinoma - pathology; Adult; Aged; Aged, 80 and over; Alectinib; Anaplastic lymphoma kinase inhibitor; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carbazoles - administration & dosage; Carcinoma, Large Cell - drug therapy; Carcinoma, Large Cell - genetics; Carcinoma, Large Cell - pathology; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - pathology; Crizotinib; Female; Follow-Up Studies; Gene Rearrangement; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Middle Aged; Neoplasm Staging; Non–small cell lung cancer; Overall survival; Piperidines - administration & dosage; Prognosis; Pyrazoles - administration & dosage; Pyridines - administration & dosage; Receptor Protein-Tyrosine Kinases - genetics; Retrospective Studies; Sequential therapy; Survival Rate; Crizotinib; Alectinib; Non–small cell lung cancer; Anaplastic lymphoma kinase inhibitor; Sequential therapy; Overall survival
• ISSN: 1556-0864; 1556-1380
• DOI: 10.1016/j.jtho.2016.07.022

Alectinib and crizotinib have been approved for the therapy of NSCLC caused by anaplastic lymphoma kinase gene (ALK) rearrangement. The effect of alectinib or crizotinib on overall survival (OS) in patients with ALK-rearranged NSCLC remains unknown. A multicenter retrospective study was conducted to compare OS between patients receiving alectinib and crizotinib and between patients treated with alectinib and those treated sequentially with crizotinib and then alectinib after crizotinib failure. The time to treatment failure (TTF), progression-free survival (PFS), and OS were compared. Sixty-one patients with ALK-rearranged NSCLC were enrolled. Forty-six patients were treated with anaplastic lymphoma kinase (ALK) inhibitors (31 with crizotinib, 28 with alectinib, and 13 with both ALK inhibitors). The response rate was 66.7% for the crizotinib-treated group and 80.8% for the alectinib-treated group. Among all patients, TTF and PFS were significantly prolonged in the alectinib-treated group compared with in the crizotinib-treated group. Subgroup analyses revealed significantly prolonged TTF for alectinib compared with crizotinib therapy in the ALK inhibitor–naive population. OS was significantly longer in the alectinib-treated group than in the crizotinib-treated group. The TTF and OS of patients treated sequentially with crizotinib and then with alectinib after crizotinib failure tended to be longer than those of patients treated with alectinib alone. Therapy with alectinib alone was significantly superior to therapy with crizotinib alone in terms of TTF, PFS, and OS, and sequential therapy with crizotinib and alectinib after crizotinib failure tended to provide a better OS benefit than did therapy with alectinib alone in patients with ALK-positive NSCLC. However, large-scale prospective studies are needed to confirm these observations.