Tamura Tomohide, Kiura Katsuyuki, Seto Takashi, Nakagawa Kazuhiko, Maemondo Makoto, Inoue Akira, Hida Toyoaki, Yoshioka Hiroshige, Harada Masao, Ohe Yuichiro, Nogami Naoyuki, Murakami Haruyasu, Kuriki Hiroshi, Shimada Tadashi, Tanaka Tomohiro, Takeuchi Kengo, Nishio Makoto
Tomohide Tamura, St Luke's International Hospital; Yuichiro Ohe, National Cancer Center Hospital; Hiroshi Kuriki, Tadashi Shimada, and Tomohiro Tanaka, Chugai Pharmaceutical; Kengo Takeuchi, Japanese Foundation for Cancer Research; Makoto Nishio, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo; Katsuyuki Kiura, Okayama University Hospital, Okayama; Takashi Seto, National Kyusyu Cancer Center, Fukuoka; Kazuhiko Nakagawa, Kindai University, Osaka-Sayama; Makoto Maemondo, Miyagi Cancer Center, Natori; Akira Inoue, Tohoku University, Sendai; Toyoaki Hida, Aichi Cancer Center, Nagoya; Hiroshige Yoshioka, Kurashiki Central Hospital, Kurashiki; Masao Harada, Hokkaido Cancer Center, Sapporo; Naoyuki Nogami, National Hospital Organization Shikoku Cancer Center, Matsuyama; and Haruyasu Murakami, Shizuoka Cancer Center, Shizuoka, Japan.
J Clin Oncol. 2017 May 10;35(14):1515-1521. doi: 10.1200/JCO.2016.70.5749. Epub 2017 Mar 15.
Purpose Alectinib is an anaplastic lymphoma kinase (ALK) -specific kinase inhibitor that seems to be effective against non-small-cell lung cancer (NSCLC) with a variety of ALK mutations. The primary analysis of AF-001JP reported a promising overall response rate. To assess progression-free survival (PFS) and overall survival (OS), patients from the phase II part of AF-001JP were followed up for approximately 3 years. Patients and Methods Oral alectinib 300 mg was administered twice per day to patients with ALK inhibitor-naïve, ALK-positive NSCLC who had progressed after one or more regimens of previous chemotherapy. In this long-term follow-up, efficacy (PFS, OS), correlation between tumor shrinkage and PFS, safety of alectinib, and relief of cancer symptoms were evaluated. Results At the updated data cutoff (September 10, 2015; first patient in August 30, 2011, last patient in April 18, 2012), 25 of 46 phase II patients were still receiving alectinib. Disease progression was confirmed in 18 patients (39%); median PFS was not reached (3-year PFS rate, 62%; 95% CI, 45 to 75). Fourteen patients had brain metastases at baseline; of these, 6 remained in the study without CNS and systemic progression. Tumor shrinkage and PFS showed no correlation. The 3-year OS rate was 78% (13 events). The most common treatment-related adverse event (all grades) was increased blood bilirubin (36.2%). Most cancer symptoms were relieved early, and medication for symptoms was dramatically decreased during alectinib therapy. Conclusion Alectinib was effective in this 3-year follow-up with a favorable safety profile over a long administration period in ALK-positive NSCLC without previous ALK inhibitor treatment.
目的 阿来替尼是一种间变性淋巴瘤激酶（ALK）特异性激酶抑制剂，似乎对具有多种ALK突变的非小细胞肺癌（NSCLC）有效。AF-001JP的初步分析报告了有前景的总缓解率。为评估无进展生存期（PFS）和总生存期（OS），对AF-001JP II期部分的患者进行了约3年的随访。
患者与方法 对于既往接受过一种或多种化疗方案后病情进展、未接受过ALK抑制剂治疗的ALK阳性NSCLC患者，口服阿来替尼300mg，每日两次。在此次长期随访中，评估了疗效（PFS、OS）、肿瘤缩小与PFS之间的相关性、阿来替尼的安全性以及癌症症状的缓解情况。
结果 在更新的数据截止日期（2015年9月10日；首例患者于2011年8月30日入组，最后一例患者于2012年4月18日入组）时，46例II期患者中有25例仍在接受阿来替尼治疗。18例患者（39%）确认疾病进展；中位PFS未达到（3年PFS率为62%；95%CI，45至75）。14例患者基线时存在脑转移；其中6例仍在研究中，无中枢神经系统和全身进展。肿瘤缩小与PFS无相关性。3年OS率为78%（13例事件）。最常见的治疗相关不良事件（所有级别）是血胆红素升高（36.2%）。大多数癌症症状早期得到缓解，在阿来替尼治疗期间症状用药显著减少。
结论 在此次3年随访中，阿来替尼对未接受过ALK抑制剂治疗的ALK阳性NSCLC患者有效，在长期给药期间具有良好的安全性。
