Sun Min Lim, Hye Ryun Kim, Hyo Sup Shim, Joo-Hang Kim, and Byoung Chul Cho, Yonsei University College of Medicine; Yun-Gyoo Lee, Yoon La Choi, and Myung-Ju Ahn, Sungkyunkwan University School of Medicine; Bong-Seog Kim, VHS Medical Center; Min Jeong Lee and Maria Kim, Yonsei University Health System, Seoul; Jong-Seok Lee and Jin-Haeng Chung, Seoul National University Bundang Hospital, Bundang; Ki Hyeong Lee, Chungbuk National University, Cheongju; Young Joo Min, University of Ulsan College of Medicine, Ulsan; Eun Kyung Cho, Gachon Medical School, Inchon; Sung Sook Lee, Inje University College of Medicine; Moon Young Choi, Inje University, Busan; Jin-Haeng Chung, Seoul National University College of Medicine, Seongnam, Republic of Korea; and Siraj M. Ali, Foundation Medicine, Cambridge, MA.
J Clin Oncol. 2017 Aug 10;35(23):2613-2618. doi: 10.1200/JCO.2016.71.3701. Epub 2017 May 18.
Purpose ROS1 rearrangement is a distinct molecular subset of non-small-cell lung cancer (NSCLC). We investigated the efficacy and safety of ceritinib in patients with ROS1-rearranged NSCLC. Patients and Methods We enrolled 32 patients with advanced NSCLC who tested positive for ROS1 rearrangement by fluorescent in situ hybridization. Ceritinib 750 mg was administered once daily. The primary end point was objective response rate. The secondary end points were disease control rate; duration of response; progression-free survival; overall survival; toxicity; and concordance among fluorescent in situ hybridization, immunohistochemistry, and next-generation sequencing. Results Between June 7, 2013, and February 1, 2016, 404 patients underwent ROS1 prescreening, and 32 patients with ROS1 rearrangement were enrolled. All patients except two were crizotinib-naïve. At the time of data cutoff, the median follow-up was 14.0 months, and 18 patients (56%) had discontinued treatment. Of the 32 patients enrolled, 28 were evaluable for response by independent radiologic review. Objective response rate was 62% (95% CI, 45% to 77%), with one complete response and 19 partial responses; duration of response was 21.0 months (95% CI, 17 to 25 months); and disease control rate was 81% (95% CI, 65% to 91%). The median progression-free survival was 9.3 months (95% CI, 0 to 22 months) for all patients and 19.3 months (95% CI, 1 to 37 months) for crizotinib-naïve patients. The median overall survival was 24 months (95% CI, 5 to 43 months). Of the eight patients with brain metastases, intracranial disease control was reported in five (63%; 95% CI, 31% to 86%). The most common adverse events (majority, grade 1 or 2) for all treated patients were diarrhea (78%), nausea (59%), and anorexia (56%). Conclusion Ceritinib demonstrated potent clinical activity in patients with ROS1-rearranged NSCLC who were heavily treated previously with multiple lines of chemotherapy.
ROS1 重排是一种非小细胞肺癌（NSCLC）的独特分子亚型。我们研究了克唑替尼在 ROS1 重排的 NSCLC 患者中的疗效和安全性。
患者和方法
我们纳入了 32 名经荧光原位杂交检测为 ROS1 重排阳性的晚期 NSCLC 患者。患者每日口服 750mg 塞瑞替尼。主要终点为客观缓解率。次要终点为疾病控制率、缓解持续时间、无进展生存期、总生存期、毒性以及荧光原位杂交、免疫组化和下一代测序之间的一致性。
结果
2013 年 6 月 7 日至 2016 年 2 月 1 日，404 名患者进行了 ROS1 预筛选，其中 32 名 ROS1 重排患者入组。除 2 名患者外，其余均为克唑替尼初治。数据截止时，中位随访时间为 14.0 个月，18 名患者（56%）已停止治疗。32 名入组患者中，28 名患者经独立影像学评估可评价疗效。客观缓解率为 62%（95%CI，45%至 77%），包括 1 例完全缓解和 19 例部分缓解；缓解持续时间为 21.0 个月（95%CI，17 至 25 个月）；疾病控制率为 81%（95%CI，65%至 91%）。所有患者的中位无进展生存期为 9.3 个月（95%CI，0 至 22 个月），克唑替尼初治患者的中位无进展生存期为 19.3 个月（95%CI，1 至 37 个月）。中位总生存期为 24 个月（95%CI，5 至 43 个月）。8 名脑转移患者中，5 名（63%；95%CI，31%至 86%）颅内疾病得到控制。所有接受治疗的患者中最常见的不良反应（多数为 1 级或 2 级）为腹泻（78%）、恶心（59%）和厌食（56%）。
结论
塞瑞替尼在先前接受过多线化疗的 ROS1 重排的 NSCLC 患者中具有显著的临床疗效。
