title: Sequential Therapy with Crizotinib and Alectinib in ALK-Rearranged Non-Small Cell Lung Cancer-A Multicenter Retrospective Study.
abstract: 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.
authors: Respiratory Center, Matsusaka Municipal Hospital, Matsusaka, Japan.
authors: Kentaro
authors: K
authors: Ito
authors: Respiratory Center, Matsusaka Municipal Hospital, Matsusaka, Japan.
authors: Osamu
authors: O
authors: Hataji
authors: Department of Respiratory Medicine, Suzuka Central General Hospital, Suzuka, Japan.
authors: Hiroyasu
authors: H
authors: Kobayashi
authors: Department of Pulmonary Medicine, Mie Prefectural General Medical Center, Yokkaichi, Japan.
authors: Atsushi
authors: A
authors: Fujiwara
authors: Department of Pulmonary Medicine, Mie Prefectural General Medical Center, Yokkaichi, Japan.
authors: Masamichi
authors: M
authors: Yoshida
authors: Department of Immunology, Mie University Faculty and Graduate School of Medicine, Tsu, Japan.
authors: Corina N
authors: CN
authors: D'Alessandro-Gabazza
authors: Department of Respiratory Medicine, Ise Red Cross Hospital, Ise, Japan.
authors: Hidetoshi
authors: H
authors: Itani
authors: Department of Respiratory Medicine, Ise Red Cross Hospital, Ise, Japan.
authors: Motoaki
authors: M
authors: Tanigawa
authors: Department of Respiratory Medicine, Yokkaichi Municipal Hospital, Yokkaichi, Japan.
authors: Takuya
authors: T
authors: Ikeda
authors: Department of Pulmonary and Critical Care Medicine, Mie University, Tsu, Japan.
authors: Kentaro
authors: K
authors: Fujiwara
authors: Department of Pulmonary and Critical Care Medicine, Mie University, Tsu, Japan.
authors: Hajime
authors: H
authors: Fujimoto
authors: Department of Pulmonary and Critical Care Medicine, Mie University, Tsu, Japan.
authors: Tetsu
authors: T
authors: Kobayashi
authors: Department of Immunology, Mie University Faculty and Graduate School of Medicine, Tsu, Japan. Electronic address: gabazza@doc.medic.mie-u.ac.jp.
authors: Esteban C
authors: EC
authors: Gabazza
authors: Mie University Center for Physical and Mental Health, Mie University, Tsu, Japan.
authors: Osamu
authors: O
authors: Taguchi
authors: Third Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan.
authors: Nobuyuki
authors: N
authors: Yamamoto
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002227:Carbazoles / Q000008:administration & dosage; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000077547:Crizotinib; D005260:Female; D005500:Follow-Up Studies; D015321:Gene Rearrangement; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010880:Piperidines / Q000008:administration & dosage; D011379:Prognosis; D011720:Pyrazoles / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D002227:Carbazoles; D010880:Piperidines; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; C582670:alectinib
keywords: Alectinib; Anaplastic lymphoma kinase inhibitor; Crizotinib; Non–small cell lung cancer; Overall survival; Sequential therapy