Lungen Clinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany.
David Geffen School of Medicine, UCLA, Los Angeles, CA.
Clin Lung Cancer. 2018 May;19(3):213-220.e4. doi: 10.1016/j.cllc.2017.11.003. Epub 2017 Nov 21.
Despite the likelihood of an initial response to an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), EGFR-mutant non-small-cell lung cancer (NSCLC) patients develop disease progression. Antiangiogenic agents in combination with an EGFR TKI might provide additional benefit in patients with EGFR-mutant NSCLC. In this article we report safety, exposure, and progression-free survival (PFS) results for part A (phase Ib) of RELAY, a randomized, double-blind, phase Ib/III study investigating safety and efficacy of erlotinib (EGFR TKI) with ramucirumab (anti-vascular endothelial growth factor receptor-2 antibody) or placebo in first-line EGFR-mutant stage IV NSCLC.
Eligible patients had untreated stage IV NSCLC, Eastern Cooperative Oncology Group performance status of 0 to 1, and activating EGFR mutation (exon 19 deletion or exon 21 L858R substitution). Patients received ramucirumab 10 mg/kg on day 1 of a repeating 14-day cycle and erlotinib 150 mg/d. Treatment continued until disease progression or unacceptable toxicity. The primary objective was to assess safety and tolerability, in terms of dose-limiting toxicities (DLTs), during the first 2 cycles.
Fourteen patients were treated and 12 were evaluable for DLTs. One patient experienced a DLT of Grade 3 elevated alanine aminotransferase during the DLT assessment period. Adverse events were reported in all patients, but were generally mild and manageable. The most common Grade 3 adverse events were hypertension, rash, and diarrhea. No serious or Grade 4 to 5 events occurred. Median PFS was 17.1 months (95% confidence interval, 8.8-not reached). Five patients continue receiving study treatment.
Ramucirumab with erlotinib showed no unexpected toxicities and encouraging clinical activity in part A. Phase III enrollment has been initiated, maintaining ramucirumab 10 mg/kg every 2 weeks with erlotinib 150 mg/d.
尽管表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKI）治疗可能会产生初始应答，但 EGFR 突变型非小细胞肺癌（NSCLC）患者会出现疾病进展。抗血管生成药物与 EGFR TKI 联合应用可能会为 EGFR 突变型 NSCLC 患者带来额外获益。本文报道了 RELAY 研究的 A 部分（Ib 期）的安全性、暴露量和无进展生存期（PFS）结果。该研究为一项随机、双盲、Ib/III 期研究，旨在评估厄洛替尼（EGFR TKI）联合或不联合雷莫芦单抗（抗血管内皮生长因子受体-2 抗体）治疗初治 EGFR 突变型 IV 期 NSCLC 的安全性和疗效。
符合条件的患者为未经治疗的 IV 期 NSCLC 患者，东部肿瘤协作组体能状态为 0-1 分，且存在激活型 EGFR 突变（外显子 19 缺失或外显子 21 L858R 取代）。患者接受雷莫芦单抗 10mg/kg，每 14 天重复 1 次，厄洛替尼 150mg/d。治疗持续至疾病进展或出现无法耐受的毒性。主要研究目标是评估前 2 个周期的安全性和耐受性，包括剂量限制性毒性（DLTs）。
14 例患者接受治疗，12 例患者可评估 DLT。1 例患者在 DLT 评估期间出现 3 级丙氨酸氨基转移酶升高的 DLT。所有患者均发生不良事件，但通常为轻度且可管理。最常见的 3 级不良事件为高血压、皮疹和腹泻。无严重或 4 级-5 级事件发生。中位 PFS 为 17.1 个月（95%置信区间，8.8-未达到）。5 例患者继续接受研究治疗。
厄洛替尼联合雷莫芦单抗在 A 部分未观察到新的毒性作用，且具有令人鼓舞的临床活性。已开始进行 III 期入组，维持雷莫芦单抗 10mg/kg 每 2 周联合厄洛替尼 150mg/d。
