Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
Jpn J Clin Oncol. 2020 May 5;50(5):594-601. doi: 10.1093/jjco/hyaa019.
Since the first discovery of rearranged during transfection (RET) fusion in lung adenocarcinoma in 2011, two tyrosine kinase inhibitors, namely vandetanib and cabozantinib, are currently available. Despite favorable outcomes in systemic control, the intracranial therapeutic response remains insufficient. In this study, the clinical characteristics and outcomes of non-small cell lung cancer (NSCLC) patients with RET rearrangements were analyzed.
Patients with NSCLC harboring RET fusion who received treatment between January 2006 and January 2018 were analyzed. RET rearrangement was identified by FISH or NGS.
A total of 59 patients were identified. About half of the patients were female (47.5%) and never smokers (50.9%). Most patients had adenocarcinoma (89.8%). A total of 17 patients (28.8%) had an intracranial lesion at the initial diagnosis of stage IV disease, and 11 additional patients (18.6%) developed intracranial metastases during follow-up. The median time to development of intracranial metastases was 19.0 months (95% CI: 9.6-28.5), resulting in a >60% cumulative incidence of brain metastasis at 24 months. The systemic efficacy of pemetrexed-based regimens was favorable with progression-free survival of 9.0 (95% CI: 6.9-11.2) and OS of 24.1 (95% CI: 15.2-33.0) months. The median progression-free survival for vandetanib and immunotherapy was 2.9 (95% CI: 2.0-3.8) and 2.1 (95% CI: 1.6-2.6) months, respectively.
Given the likelihood of RET-rearranged NSCLC progressing to intracranial metastases and the absence of apparent clinical benefit of currently available targeted or immunotherapeutic agents, development of novel treatment with higher selectivity and better penetration of the blood-brain barrier remains a priority.
自 2011 年首次发现肺腺癌中的转染重排（RET）融合以来，已有两种酪氨酸激酶抑制剂，即凡德他尼和卡博替尼，可用于临床。尽管全身控制效果良好，但颅内治疗反应仍不理想。本研究分析了携带 RET 重排的非小细胞肺癌（NSCLC）患者的临床特征和结局。
分析了 2006 年 1 月至 2018 年 1 月期间接受治疗的 NSCLC 患者中存在 RET 融合的患者。通过 FISH 或 NGS 确定 RET 重排。
共确定了 59 例患者。约一半的患者为女性（47.5%）和从不吸烟（50.9%）。大多数患者为腺癌（89.8%）。在 IV 期疾病的初始诊断时，共有 17 例（28.8%）患者存在颅内病变，在随访期间又有 11 例（18.6%）患者发生颅内转移。颅内转移的中位时间为 19.0 个月（95%CI：9.6-28.5），导致 24 个月时脑转移的累积发生率超过 60%。培美曲塞为基础的方案的系统疗效良好，无进展生存期为 9.0（95%CI：6.9-11.2），总生存期为 24.1（95%CI：15.2-33.0）个月。凡德他尼和免疫治疗的中位无进展生存期分别为 2.9（95%CI：2.0-3.8）和 2.1（95%CI：1.6-2.6）个月。
鉴于存在 RET 重排 NSCLC 进展为颅内转移的可能性，以及目前可用的靶向或免疫治疗药物无明显临床获益，开发具有更高选择性和更好血脑屏障穿透性的新型治疗方法仍然是当务之急。
