Background: Crizotinib is an oral small-molecule tyrosine kinase inhibitor, which was approved in the United States (US) in August of 2011 for the treatment of anaplastic lymphoma kinase (ALK) - positive advanced non-small cell lung cancer (NSCLC). There is currently limited data on crizotinib treatment and related outcomes in ALK-positive advanced NSCLC patients with brain metastases at diagnosis in real world settings. The main objective of the current analyses was to assess and report the response rates in the ALK- positive advanced lung cancer patients with brain metastases treated with crizotinib in regular clinical practice.
Methods: Physicians in the US (N= 107) and Canada (N= 40) were recruited from cancer centers or teaching hospitals (48%) or free standing oncology clinics (47%) to abstract data retrospectively from medical records of adult (greater than or equal to 18 years) patients diagnosed with ALK-positive advanced NSCLC and treated with crizotinib as first-or later-line therapy from 8/1/2011-3/31/2013 (for the US) or 4/12012-3/31/2013 (for Canada) in non-clinical trial settings. IRB approval was obtained. A secure web-based form was used by physicians to abstract data and all patient data were de-identified and anonymous. Descriptive analyses were conducted to summarize objective response rate (ORR) in the subgroup with brain metastases. One-year survival rates from initiation of crizotinib were descriptively analyzed for the sub group with brain metastases using the Kaplan-Meier method.
Results: Data were extracted from 212 patient records in US (N=147) and Canada (N=65), which included 33 ALK-positive advanced NSCLC patients with brain metastases present prior to crizotinib initiation. The mean (SD) patient age at diagnosis for these 33 patients was 57.4 (12.0) years and a majority were male (58%), Caucasian (76%), current or former smokers (67%), ECOG status 0 or 1 (55%), adenocarcinoma histology (85%) and initially diagnosed at the locally advanced or metastatic stage (70%). The majority (71%) of these patients had been treated with either whole brain radiotherapy (16 patients) or stereotactic radiosurgery (8 patients) prior to initiation of crizotinib treatment. Of these 33 patients, 21 received crizotinib as 1st line therapy for advanced ALK-positive NSCLC. Approximately 61% were alive at time of medical record data abstraction. The ORR was estimated to be 61% and 60% for these patients with brain metastases who received crizotinib as 1st and later line treatment, respectively. The Kaplan-Meier estimates of 1-year survival from crizotinib initiation were 81% and 77% in patients with brain metastases, who received crizotinib as 1st line and later line treatment, respectively.
Conclusion: In ALK- positive advanced NSCLC patients with brain metastases, complete or partial response was reported in majority of patients during treatment with crizotinib in real world settings.
