Efficacy and tolerability of crizotinib in the treatment of ALK-positive, advanced non-small cell lung cancer in Chinese patients

Abstract

Crizotinib has been reported to be particularly effective and to have acceptable toxicity in advanced anaplastic lymphoma kinase (ALK)-positive, non-small cell lung cancer (NSCLC). In this study, we analyzed the efficacy and tolerability of crizotinib in the treatment of 72 Chinese patients with ALK-positive, advanced NSCLC. All patients received oral crizotinib 250 mg twice daily in 28-day cycles during the period June 1, 2013, to October 15, 2014. The tumor response was assessed after the first cycle of crizotinib and then after every two cycles using the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.0. Tolerability was assessed at least twice per cycle until crizotinib was discontinued. The patients tended to be young (mean age 55 years, range 31-83 years), never or light smokers (smoking index <400), and to have an adenocarcinoma histology. Most (49/72; 68.1 %) had received previous anticancer treatment before crizotinib therapy. Sixty-seven patients (93 %) were able to be assessed for efficacy. The objective response rate and disease control rate were 52.2 % (95 % CI 40.5-63.9 %) and 64.2 % (95 % CI 52.75-75.7 %), respectively. The estimated median progression-free survival for all 67 patients was 10.3 months (95 % CI 8.6-12.0 months). Mild visual disturbances, nausea, vomiting, diarrhea and constipation were the most commonly reported adverse effects. Thus, crizotinib was well tolerated and showed promising efficacy in Chinese patients with ALK-positive, advanced NSCLC. Further prospective, multicenter studies with a larger sample size are needed to confirm these findings.

Use of capture-based next-generation sequencing to detect ALK fusion in plasma cell-free DNA of patients with non-small-cell lung cancer

“…Consistent with previously reported results [16–18], our study indicated that patients who were ALK -positive were predominantly young, never smokers, and had an adenocarcinoma histology. The occurrence of ALK gene rearrangements, which are present in about 5% of patients with NSCLC, is relatively rare compared with epidermal growth factor receptor (EGFR) mutations [1, 19].…”

Efficacy of Crizotinib, Ceritinib, and Alectinib in ALK-Positive Non-Small Cell Lung Cancer Treatment: A Meta-Analysis of Clinical Trials

“…The reasons for exclusion were not relevant (n = 50), retrospective chart reviews (n = 7), no specific data for outcome measures (n = 7), no sufficient ALK-positive NSCLC (n = 3), data overlapping (n = 16), and no available data on results (n = 5). A total of 20 clinical trials were included in the final analysis with 18 studies [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]26,28,29] in English and two studies [25,27] in Chinese.…”

“…Except for 13 global multicenter trials [10,11,14,[16][17][18][19][20][21][22][23][24]29], the seven remaining studies were conducted in China [12,[25][26][27] and Japan [13,15,28]. Four studies [10,12,21,26] (1344 patients), three studies [11,16,28] (406 patients), and three studies [14,15,23] (243 patients) used a single arm design for the efficacy of crizotinib, ceritinib, and alectinib, respectively. Five studies [18][19][20]25,27] (967 patients), two studies [22,24] (607 patients), one study [29] (72 patients), and two studies [13,17] (510 patients) investigated the efficacy of crizotinib versus chemotherapy, ceritinib versus chemotherapy, alectinib versus chemotherapy, and alectinib versus crizotinib, respectively.…”

“…Since the initial development of ALK inhibitors, subsequent clinical trials on the efficacy of the ALK inhibitors have been published [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29]. Several systematic reviews and meta-analyses have also been reported [30][31][32][33].…”

Pooled safety analyses of ALK-TKI inhibitor in ALK-positive NSCLC

“…[16]Crizotinib171NA2419553423NANAChaigneau, A. [4]Ceritinib1021000000000Cui, S. [17]Crizotinib72103000500000Felip, E. [5]Ceritinib124NA17NANANANANANANANANAMok, T. [6]Ceritinib1406422NANANA698NANANACui, S. [18]Crizotinib5682000500000Kim, D. W. [7]Ceritinib24612573010121115150816Ou, Sai-Hong [8]Alectinib138382NA411100NANAShaw, A. T. [9]Alectinib87355130000000Zhang, Q. [19]Crizotinib711000000000…”