Kiura Katsuyuki, Imamura Fumio, Kagamu Hiroshi, Matsumoto Shingo, Hida Toyoaki, Nakagawa Kazuhiko, Satouchi Miyako, Okamoto Isamu, Takenoyama Mitsuhiro, Fujisaka Yasuhito, Kurata Takayasu, Ito Masayuki, Tokushige Kota, Hatano Ben, Nishio Makoto
Okayama University Hospital, Okayama.
Osaka International Cancer Institute, Osaka.
Jpn J Clin Oncol. 2018 Apr 1;48(4):367-375. doi: 10.1093/jjco/hyy016.
In the global, Phase 3, ASCEND-5 study, ceritinib improved progression-free survival (PFS) vs chemotherapy in patients with anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) who had previously progressed on crizotinib and platinum-based chemotherapy. Here, we report efficacy and safety in a subset of Japanese patients from the ASCEND-5 study.
Patients with advanced ALK-rearranged NSCLC received oral ceritinib 750 mg/day or chemotherapy (intravenous pemetrexed 500 mg/m2 or docetaxel 75 mg/m2 [investigator's choice], every 21 days).
Among the 231 patients, 29 were Japanese, of which, 11 were treated with ceritinib and 18 were treated with chemotherapy (5 with pemetrexed and 13 with docetaxel). All the patients received prior crizotinib and one or two lines of prior chemotherapy for advanced disease. Median follow-up time was 16.6 months for ceritinib arm and 16.4 months for chemotherapy arm in the overall population. The median PFS by blinded independent review committee was 9.8 months (95% CI, 4.3-14.0) in ceritinib arm vs 1.6 months (95% CI, 1.4-3.0) in chemotherapy arm. Grade 3 or 4 adverse events, suspected to be study drug related, were reported in 36.4% of ceritinib arm and 72.2% of chemotherapy arm, respectively. No Grade 3 or 4 events of diarrhea, nausea and vomiting were reported in both the treatment arms. Adverse events leading to study drug discontinuation were reported in one patient in each arm: Grade 3 central-nervous system metastases in ceritinib-treated patient and Grade 3 febrile neutropenia in chemotherapy-treated patient.
Consistent with overall population, ceritinib demonstrated better efficacy compared with the standard second-line chemotherapy in Japanese patients with crizotinib-resistant ALK+ NSCLC.
CLINICALTRIALS.GOV IDENTIFIER: NCT01828112.
在一项全球性3期ASCEND - 5研究中，对于既往接受克唑替尼和铂类化疗后病情进展的间变性淋巴瘤激酶（ALK）重排的非小细胞肺癌（NSCLC）患者，色瑞替尼较化疗可改善无进展生存期（PFS）。在此，我们报告ASCEND - 5研究中日本患者亚组的疗效和安全性。
晚期ALK重排NSCLC患者接受口服色瑞替尼750 mg/天或化疗（静脉注射培美曲塞500 mg/m²或多西他赛75 mg/m²[研究者选择]，每21天一次）。
在231例患者中，29例为日本患者，其中11例接受色瑞替尼治疗，18例接受化疗（5例接受培美曲塞，13例接受多西他赛）。所有患者均接受过克唑替尼治疗以及针对晚期疾病的一线或二线化疗。总体人群中，色瑞替尼组的中位随访时间为16.6个月，化疗组为16.4个月。经盲态独立审查委员会评估，色瑞替尼组的中位PFS为9.8个月（95%CI，4.3 - 14.0），化疗组为1.6个月（95%CI，1.4 - 3.0）。分别有36.4%的色瑞替尼组患者和72.2%的化疗组患者报告了疑似与研究药物相关的3级或4级不良事件。两个治疗组均未报告3级或4级腹泻、恶心和呕吐事件。每个治疗组均有1例患者报告了导致研究药物停用的不良事件：色瑞替尼治疗的患者出现3级中枢神经系统转移，化疗治疗的患者出现3级发热性中性粒细胞减少。
与总体人群一致，在对克唑替尼耐药的ALK + NSCLC日本患者中，色瑞替尼的疗效优于标准二线化疗。
NCT01828112。
