Illini Oliver, Hochmair Maximilian Johannes, Fabikan Hannah, Weinlinger Christoph, Tufman Amanda, Swalduz Aurélie, Lamberg Kristina, Hashemi Sayed M S, Huemer Florian, Vikström Anders, Wermke Martin, Absenger Gudrun, Addeo Alfredo, Banerji Shantanu, Calles Antonio, Clarke Stephen, Di Maio Massimo, Durand Alice, Duruisseaux Michaël, Itchins Malinda, Kääränien Okko-Sakari, Krenn Florian, Laack Eckart, de Langen Adrianus Johannes, Mohorcic Katja, Pall Georg, Passaro Antonio, Prager Gerald, Rittmeyer Achim, Rothenstein Jeffrey, Schumacher Michael, Wöll Ewald, Valipour Arschang
Department of Respiratory and Critical Care Medicine, Karl Landsteiner Institute for Lung Research and Pulmonary Oncology, Klinik Floridsdorf, Brünner Strasse 68, Vienna, 1210, Austria.
Department of Respiratory and Critical Care Medicine, Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Klinik Floridsdorf, Vienna, Austria.
Ther Adv Med Oncol. 2021 Jun 11;13:17588359211019675. doi: 10.1177/17588359211019675. eCollection 2021.
Rearranged during transfection (RET) gene fusions are rare genetic drivers in non-small cell lung cancer (NSCLC). Selective RET-inhibitors such as selpercatinib have shown therapeutic activity in early clinical trials; however, their efficacy in the real-world setting is unknown.
A retrospective efficacy and safety analysis was performed on data from RET fusion-positive NSCLC patients who participated in a selpercatinib access program (named patient protocol) between August 2019 and January 2021.
Data from 50 patients with RET fusion-positive advanced NSCLC treated with selpercatinib at 27 centers in 12 countries was analyzed. Most patients were Non-Asian (90%), female (60%), never-smokers (74%), with a median age of 65 years (range, 38-89). 32% of the patients had known brain metastasis at the time of selpercatinib treatment. Overall, 13 patients were treatment-naïve, while 37 were pretreated with a median of three lines of therapy (range, 1-8). The objective response rate (ORR) was 68% [95% confidence interval (CI), 53-81] in the overall population. The disease control rate was 92%. The median progression-free survival was 15.6 months (95% CI, 8.8-22.4) after a median follow-up of 9 months. In patients with measurable brain metastases ( = 8) intracranial ORR reached 100%. In total, 88% of patients experienced treatment-related adverse events (TRAEs), a large majority of them being grade 1 or 2. The most common grade ⩾ 3 TRAEs were increased liver enzyme levels (in 10% of patients), prolonged QTc time (4%), abdominal pain (4%), hypertension (4%), and fatigue/asthenia (4%). None of patients discontinued selpercatinib treatment for safety reasons. No new safety concerns were observed, nor where there any treatment-related death.
In this real-world setting, the selective RET-inhibitor selpercatinib demonstrated durable systemic and intracranial antitumor activity in RET fusion-positive NSCLC and was well tolerated.
转染期间重排（RET）基因融合是非小细胞肺癌（NSCLC）中罕见的基因驱动因素。选择性RET抑制剂如塞尔帕替尼在早期临床试验中已显示出治疗活性；然而，其在现实环境中的疗效尚不清楚。
对2019年8月至2021年1月期间参加塞尔帕替尼准入计划（名为患者方案）的RET融合阳性NSCLC患者的数据进行回顾性疗效和安全性分析。
分析了来自12个国家27个中心接受塞尔帕替尼治疗的50例RET融合阳性晚期NSCLC患者的数据。大多数患者为非亚洲人（90%），女性（60%），从不吸烟者（74%），中位年龄为65岁（范围38 - 89岁）。32%的患者在接受塞尔帕替尼治疗时已知有脑转移。总体而言，13例患者未接受过治疗，37例患者接受过预处理，中位治疗线数为三线（范围1 - 8线）。总体人群的客观缓解率（ORR）为68%[95%置信区间（CI），53 - 81]。疾病控制率为92%。中位随访9个月后，中位无进展生存期为15.6个月（95%CI，8.8 - 22.4）。在有可测量脑转移的患者（n = 8）中，颅内ORR达到100%。总共88%的患者经历了治疗相关不良事件（TRAEs），其中大多数为1级或2级。最常见的≥3级TRAEs为肝酶水平升高（10%的患者）、QTc时间延长（4%）、腹痛（4%）、高血压（4%）和疲劳/乏力（4%）。没有患者因安全原因停用塞尔帕替尼治疗。未观察到新的安全问题，也没有与治疗相关的死亡。
在这一现实环境中，选择性RET抑制剂塞尔帕替尼在RET融合阳性NSCLC中显示出持久的全身和颅内抗肿瘤活性，且耐受性良好。
