Department of Clinical Oncology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.
Department of Respiratory Medicine, Graduate School of Medicine, Osaka City University, Osaka, Japan.
Invest New Drugs. 2021 Dec;39(6):1598-1603. doi: 10.1007/s10637-021-01147-w. Epub 2021 Jul 2.
The study was designed to investigate the safety of ramucirumab administered in combination with erlotinib or osimertinib for patients with untreated EGFR-mutated non-small cell lung cancer (NSCLC) and asymptomatic brain metastases, a patient subgroup in which these regimens have remained untested.
This phase 1b study (RELAY-Brain) consisted of two cohorts with three patients each. Patients with asymptomatic brain metastases received ramucirumab every 2 weeks plus either daily oral erlotinib or osimertinib until disease progression or intolerable toxicity. The primary objective was to assess dose-limiting toxicity (DLT), defined as central nervous system (CNS) hemorrhage of grade ≥ 2.
Six patients were enrolled. Neither DLT nor serious or unexpected adverse events were observed. One treatment-related adverse event of grade ≥ 3 (hypertension of grade 3) was apparent. Common adverse events were generally manageable. The median number of ramucirumab administrations was 18.5 (range, 13 to 31), and there were no detected episodes of CNS hemorrhage. Five of the six patients showed an objective systemic response. Although only one patient had a measurable CNS lesion at baseline, a confirmed intracranial partial response was observed.
Ramucirumab in combination with erlotinib or osimertinib showed safety for EGFR-mutated NSCLC with brain metastases.
本研究旨在调查雷莫芦单抗联合厄洛替尼或奥希替尼用于未经治疗的表皮生长因子受体（EGFR）突变型非小细胞肺癌（NSCLC）和无症状脑转移患者的安全性，这些方案在该患者亚组中尚未得到检验。
这项 1b 期研究（RELAY-Brain）包括两个队列，每个队列各有 3 名患者。无症状脑转移患者接受每 2 周一次的雷莫芦单抗联合每日口服厄洛替尼或奥希替尼治疗，直至疾病进展或出现无法耐受的毒性。主要目的是评估剂量限制性毒性（DLT），定义为≥2 级的中枢神经系统（CNS）出血。
共入组 6 例患者。未观察到 DLT 或严重或意外的不良事件。有 1 例与治疗相关的不良事件为 3 级（3 级高血压）。常见的不良反应通常可以控制。雷莫芦单抗的中位给药次数为 18.5 次（范围为 13 至 31 次），未检测到 CNS 出血事件。6 例患者中有 5 例出现了客观的全身反应。尽管基线时有 1 例患者存在可测量的 CNS 病变，但观察到了确认的颅内部分缓解。
雷莫芦单抗联合厄洛替尼或奥希替尼治疗 EGFR 突变型 NSCLC 伴脑转移的安全性良好。
