Kentaro Ito1, Osamu Hataji1, Hiroyasu Kobayashi2, Atsushi Fujiwara3, Masamichi Yoshida3, Corina N D'Alessandro-Gabazza4, Hidetoshi Itani5, Motoaki Tanigawa5, Takuya Ikeda6, Kentaro Fujiwara7, Hajime Fujimoto7, Tetsu Kobayashi7, Esteban C Gabazza8, Osamu Taguchi9, Nobuyuki Yamamoto10. 1. Respiratory Center, Matsusaka Municipal Hospital, Matsusaka, Japan. 2. Department of Respiratory Medicine, Suzuka Central General Hospital, Suzuka, Japan. 3. Department of Pulmonary Medicine, Mie Prefectural General Medical Center, Yokkaichi, Japan. 4. Department of Immunology, Mie University Faculty and Graduate School of Medicine, Tsu, Japan. 5. Department of Respiratory Medicine, Ise Red Cross Hospital, Ise, Japan. 6. Department of Respiratory Medicine, Yokkaichi Municipal Hospital, Yokkaichi, Japan. 7. Department of Pulmonary and Critical Care Medicine, Mie University, Tsu, Japan. 8. Department of Immunology, Mie University Faculty and Graduate School of Medicine, Tsu, Japan. Electronic address: gabazza@doc.medic.mie-u.ac.jp. 9. Mie University Center for Physical and Mental Health, Mie University, Tsu, Japan. 10. Third Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan.
Abstract
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
INTRODUCTION: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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.