克唑替尼治疗 ROS1 重排的晚期非小细胞肺癌（NSCLC）：PROFILE 1001 研究的更新结果，包括总生存期。
Crizotinib in ROS1-rearranged advanced non-small-cell lung cancer (NSCLC): updated results, including overall survival, from PROFILE 1001.
机构信息
Department of Medicine, Massachusetts General Hospital Cancer Center, Boston.
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA.
出版信息
Ann Oncol. 2019 Jul 1;30(7):1121-1126. doi: 10.1093/annonc/mdz131.
BACKGROUND
In the ongoing phase I PROFILE 1001 study, crizotinib showed antitumor activity in patients with ROS1-rearranged advanced non-small-cell lung cancer (NSCLC). Here, we present updated antitumor activity, overall survival (OS) and safety data (additional 46.2 months follow-up) for patients with ROS1-rearranged advanced NSCLC from PROFILE 1001.
PATIENTS AND METHODS
ROS1 status was determined by FISH or reverse transcriptase-polymerase chain reaction. All patients received crizotinib at a starting dose of 250 mg twice daily.
RESULTS
Fifty-three patients received crizotinib, with a median duration of treatment of 22.4 months. At data cut-off, treatment was ongoing in 12 patients (23%). The objective response rate (ORR) was 72% [95% confidence interval (CI), 58% to 83%], including six confirmed complete responses and 32 confirmed partial responses; 10 patients had stable disease. Responses were durable (median duration of response 24.7 months; 95% CI, 15.2-45.3). ORRs were consistent across different patient subgroups. Median progression-free survival was 19.3 months (95% CI, 15.2-39.1). A total of 26 deaths (49%) occurred (median follow-up period of 62.6 months), and of the remaining 27 patients (51%), 14 (26%) were in follow-up at data cut-off. Median OS was 51.4 months (95% CI, 29.3 to not reached) and survival probabilities at 12, 24, 36, and 48 months were 79%, 67%, 53%, and 51%, respectively. No correlation was observed between OS and specific ROS1 fusion partner. Treatment-related adverse events (TRAEs) were mainly grade 1 or 2, per CTCAE v3.0. There were no grade ≥4 TRAEs and no TRAEs associated with permanent discontinuation. No new safety signals were reported with long-term crizotinib treatment.
CONCLUSIONS
These findings serve as a new benchmark for OS in ROS1-rearranged advanced NSCLC, and continue to show the clinically meaningful benefit and safety of crizotinib in this molecular subgroup.
TRIAL REGISTRATION NUMBER
ClinicalTrials.gov identifier NCT00585195.
背景
在正在进行的 I 期 PROFILE 1001 研究中，克唑替尼在 ROS1 重排的晚期非小细胞肺癌（NSCLC）患者中显示出抗肿瘤活性。在此，我们报告了来自 PROFILE 1001 的 ROS1 重排的晚期 NSCLC 患者的更新抗肿瘤活性、总生存期（OS）和安全性数据（额外 46.2 个月的随访）。
患者和方法
ROS1 状态通过 FISH 或逆转录酶-聚合酶链反应确定。所有患者均以 250mg 每日两次的起始剂量接受克唑替尼治疗。
结果
53 名患者接受了克唑替尼治疗，中位治疗时间为 22.4 个月。截至数据截止日期，12 名患者（23%）仍在接受治疗。客观缓解率（ORR）为 72%[95%置信区间（CI），58%至 83%]，包括 6 例确认的完全缓解和 32 例确认的部分缓解；10 例患者疾病稳定。缓解是持久的（缓解的中位持续时间为 24.7 个月；95%CI，15.2-45.3）。在不同的患者亚组中，ORR 是一致的。中位无进展生存期为 19.3 个月（95%CI，15.2-39.1）。共有 26 例死亡（49%）（中位随访时间为 62.6 个月），其余 27 名患者（51%）中有 14 例（26%）在数据截止日期仍在随访中。中位总生存期为 51.4 个月（95%CI，29.3 至未达到），12、24、36 和 48 个月的生存率分别为 79%、67%、53%和 51%。OS 与特定的 ROS1 融合伙伴之间无相关性。治疗相关不良事件（TRAEs）主要为 1 级或 2 级，根据 CTCAE v3.0 分级。无 3 级或 4 级 TRAE，也无因 TRAE 而永久停药的病例。长期使用克唑替尼治疗未出现新的安全性信号。
结论
这些发现为 ROS1 重排的晚期 NSCLC 的 OS 提供了新的基准，并继续显示克唑替尼在这一分子亚组中的临床获益和安全性。
临床试验注册号
ClinicalTrials.gov 标识符 NCT00585195。
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