Progression-Free and Overall Survival of Patients With ALK Rearrangement-Positive Non-Small Cell Lung Cancer Treated Sequentially With Crizotinib and Alectinib.
Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) show marked therapeutic efficacy in patients with non-small cell lung cancer (NSCLC) harboring the echinoderm microtubule-associated protein-like 4-ALK fusion gene. The effect on overall survival (OS) of sequential treatment with the first- and second-generation ALK-TKIs crizotinib and alectinib, respectively, has remained unknown. We have examined the clinical outcome of such sequential treatment in a retrospective analysis of patients with ALK-rearranged NSCLC.



Eleven patients with ALK-rearranged NSCLC treated with crizotinib followed by alectinib were identified. The progression-free survival (PFS) and OS for these patients were determined from a retrospective review of their medical records.



The median PFS on crizotinib or alectinib was 6.1 months (range, 1.0-15.4 months) and 15.2 months (range, 1.0-28.3 months), respectively. The median combined PFS for both crizotinib and alectinib was 18.2 months (range, 10.4-43.7 months). Crizotinib was continued beyond radiographic evidence of progressive disease in 6 of the 11 patients, with a median duration of postprogression crizotinib treatment of 9.4 months (range, 0-20.5 months). The OS period from the diagnosis of metastatic disease or the initiation of crizotinib treatment was 51.1 months (range, 20.9-69.5 months) and 48.6 months (range, 19.8-50.1 months), respectively.



Our retrospective study has revealed durable survival for alectinib treatment after crizotinib failure in patients with ALK-rearranged NSCLC.
Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka, Japan.
Satomi
S
Watanabe
Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka, Japan. Electronic address: hayashi_h@dotd.med.kindai.ac.jp.
Hidetoshi
H
Hayashi
Department of Medical Oncology, Kishiwada Municipal Hospital, Osaka, Japan.
Kunio
K
Okamoto
Department of Pharmacy, Kinki University Hospital, Faculty of Medicine, Osaka, Japan.
Kimiko
K
Fujiwara
Department of Medical Oncology, Izumi Municipal Hospital, Osaka, Japan.
Yoshikazu
Y
Hasegawa
Department of Medical Oncology, Kishiwada Municipal Hospital, Osaka, Japan.
Hiroyasu
H
Kaneda
Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka, Japan.
Kaoru
K
Tanaka
Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka, Japan.
Masayuki
M
Takeda
Department of Medical Oncology, Kinki University Faculty of Medicine, Osaka, Japan.
Kazuhiko
K
Nakagawa
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000401:mortality* / Q000556:secondary; D000328:Adult; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D014408:Biomarkers, Tumor / Q000235:genetics; D002227:Carbazoles / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000401:mortality* / Q000556:secondary; D000077547:Crizotinib; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015321:Gene Rearrangement; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D009367:Neoplasm Staging; D010880:Piperidines / Q000627:therapeutic use; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011720:Pyrazoles / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult
D014408:Biomarkers, Tumor; D002227:Carbazoles; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; C582670:alectinib
ALK-TKI; Anaplastic lymphoma kinase; NSCLC; OS; PFS