Goldman Jonathan W, Shi Peipei, Reck Martin, Paz-Ares Luis, Koustenis Andrew, Hurt Karla C
Department of Hematology and Oncology, UCLA Medical Center, Santa Monica, CA.
Eli Lilly and Company, Indianapolis, IN.
Clin Lung Cancer. 2016 Jan;17(1):80-4. doi: 10.1016/j.cllc.2015.08.003. Epub 2015 Aug 18.
This clinical trial summary provides the background and rationale for the JUNIPER study (NCT02152631). JUNIPER is a randomized study of abemaciclib (200 mg orally every 12 hours) with best supportive care (BSC) versus erlotinib (150 mg orally every 24 hours) with BSC in patients with stage IV non-small-cell lung cancer (NSCLC) whose tumors have detectable Kirsten rat sarcoma (KRAS) mutations and whose disease has progressed after platinum-based chemotherapy and 1 other previous therapy, or who are not eligible for further chemotherapy. Approximately 550 patients will be randomized in a 3:2 ratio and stratified according to number of previous chemotherapy regimens (1 vs. 2), Eastern Cooperative Oncology Group performance status (0 vs. 1), sex (male vs. female), and KRAS mutation (G12C vs. others). Erlotinib was chosen as the control arm, because it is the only agent indicated for second- and third-line therapy in advanced NSCLC. Treatment will continue until disease progression or unacceptable toxicity occurs, with assessments every 28 days, followed by short-term and long-term follow-up. The coprimary efficacy objectives of this study are progression-free survival (PFS) and overall survival (OS); secondary objectives are overall response rate, changes in patient-reported pain and disease-related symptoms, changes in health status, resource utilization, safety and tolerability, and pharmacokinetics/pharmacodynamics. This design has 80% power to detect OS hazard ratio (HR) of 0.75 (type I error 0.045) and PFS HR of 0.67 (type I error 0.005). If the coprimary objectives (OS and PFS) are achieved, this study will provide a new alternative third-line treatment option for patients with NSCLC whose tumors have detectable KRAS mutations.
本临床试验总结提供了JUNIPER研究（NCT02152631）的背景和原理。JUNIPER是一项随机研究，在IV期非小细胞肺癌（NSCLC）患者中，将阿贝西利（每12小时口服200mg）联合最佳支持治疗（BSC）与厄洛替尼（每24小时口服150mg）联合BSC进行对比，这些患者的肿瘤具有可检测的 Kirsten 大鼠肉瘤（KRAS）突变，且疾病在铂类化疗和另外一种先前治疗后进展，或者不符合进一步化疗的条件。约550例患者将按3:2的比例随机分组，并根据先前化疗方案的数量（1种 vs. 2种）、东部肿瘤协作组体能状态（0 vs. 1）、性别（男性 vs. 女性）和KRAS突变（G12C vs. 其他）进行分层。选择厄洛替尼作为对照臂，因为它是唯一被批准用于晚期NSCLC二线和三线治疗的药物。治疗将持续至疾病进展或出现不可接受的毒性，每28天进行评估，随后进行短期和长期随访。本研究的共同主要疗效目标是无进展生存期（PFS）和总生存期（OS）；次要目标是总缓解率、患者报告的疼痛和疾病相关症状的变化、健康状况的变化、资源利用、安全性和耐受性以及药代动力学/药效学。该设计有80%的把握度检测到OS风险比（HR）为0.75（I型错误0.045）和PFS HR为0.67（I型错误0.005）。如果实现了共同主要目标（OS和PFS），本研究将为肿瘤具有可检测KRAS突变的NSCLC患者提供一种新的三线治疗选择。
