ALK 양성 폐선암 환자에서 ALK 억제제의 효과에 대한 현실 데이터 연구

Abstract

Background: Crizotinib has shown its superiority in clinical trials compared to conventional chemotherapy in patients with anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) patient, but its use and outcomes in real-world settings are yet to be investigated. This study aimed to assess treatment patterns and outcomes of crizotinib therapy in ALK-positive NSCLC patients, as well as to seek factors associated with progression-free survival and overall survival of ALK-positive NSCLC patients. Methods: A retrospective medical record review of 176 patients who are diagnosed as metastatic or recurred NSCLC from January 1st, 2006 to June 30th, 2018 and treated with crizotinib was performed. Descriptive analyses were conducted to assess treatment patterns and objective response rate (ORR). Survival analysis to estimate progression-free survival (PFS) and overall survival (OS) was performed. Comparison of the treatment outcomes by the setting of crizotinib initiation was done. Cox regression analysis was used to find predictive factors associated with PFS and OS from initiation of crizotinib. Results: Median age was 55.7 (ranged 20 to 84) years and 85 patients (48.3%) were male. Seventy-two (40.9%) patients died at the time of analysis. Seventy-eight patients initiated crizotinib as first-line therapy. Overall response rate was 54.5% (50.0% for first-line recipients, 58.2% for second-/later-line). Median (95% CI) PFS from crizotinib initiation and OS from first dose of chemotherapeutic agent were 14.3 (11.6-17.0) and 41.7 (25.4-58.1) months, respectively. No significant difference of ORR, OS, and PFS, according to the setting of crizotinib initiation was observed. Post-progression survival was significantly longer in patients who received subsequent ALK inhibitors. Multivariate Cox analysis showed poor performance status (HR 3.472, p-value < 0.001) and number of metastatic organs (≥3, HR 1.648, p-value 0.017) were independently associated to shorter PFS and OS, while history of getting pemetrexed before use of crizotinib (HR 0.638, p-value 0.039) was independently related to longer OS. Conclusions: Outcomes for crizotinib recipients were in line with previous trials, with PFS and OS appearing more favorable. Subsequent treatment of ALK inhibitors after progression under crizotinib showed better survival outcome. Poor performance status and number of metastatic organs correlated to worse PFS and OS, while history of previous use of pemetrexed before crizotinib correlated to better OS.