卡马替尼治疗既往接受过 MET 抑制剂治疗的 MET 改变型肺癌患者的 II 期研究。
A Phase 2 Study of Capmatinib in Patients With MET-Altered Lung Cancer Previously Treated With a MET Inhibitor.
机构信息
Massachusetts General Hospital Cancer Center, Boston, Massachusetts; Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts.
Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts.
出版信息
J Thorac Oncol. 2021 May;16(5):850-859. doi: 10.1016/j.jtho.2021.01.1605. Epub 2021 Feb 3.
INTRODUCTION
Capmatinib is approved for MET exon 14-altered NSCLC on the basis of activity in targeted therapy-naive patients. We conducted a phase 2 study to assess the efficacy of capmatinib in patients previously treated with a MET inhibitor.
METHODS
Patients with advanced NSCLC harboring MET amplification or MET exon 14 skipping alterations received capmatinib 400 mg twice daily. The primary end point was the objective response rate. Secondary end points included progression-free survival, disease control rate (DCR), intracranial response rate, and overall survival. Circulating tumor DNA was analyzed to identify capmatinib resistance mechanisms.
RESULTS
A total of 20 patients were enrolled between May 2016 and November 2019, including 15 patients with MET skipping alterations and five patients with MET amplification. All patients had received crizotinib; three had also received other MET-directed therapies. The median interval between crizotinib and capmatinib was 22 days (range: 4-374). Two patients (10%) achieved an objective response to capmatinib and 14 had stable disease, yielding a DCR of 80%. Among five patients who discontinued crizotinib for intolerance, the DCR was 83%, including two patients with the best tumor shrinkage of -25% and -28%. Intracranial DCR among four patients with measurable brain metastases was 100%, with no observed intracranial objective responses. Overall, the median progression-free survival and overall survival were 5.5 (95% confidence interval: 1.3-11.0) and 11.3 (95% confidence interval: 5.5-not reached) months, respectively. MET D1228 and Y1230 mutations and MAPK alterations were recurrently detected in postcrizotinib, precapmatinib plasma. New and persistent MET mutations and MAPK pathway alterations were detected in plasma at progression on capmatinib.
CONCLUSIONS
Capmatinib has modest activity in crizotinib-pretreated MET-altered NSCLC, potentially owing to overlapping resistance mechanisms.
简介
卡马替尼获批用于 MET 外显子 14 改变的非小细胞肺癌，基于其在初治患者中的靶向治疗活性。我们开展了一项 2 期研究，以评估卡马替尼在先前接受过 MET 抑制剂治疗的患者中的疗效。
方法
晚期 NSCLC 患者存在 MET 扩增或 MET 外显子 14 跳跃改变，接受卡马替尼 400 mg，每日两次。主要终点为客观缓解率。次要终点包括无进展生存期、疾病控制率（DCR）、颅内缓解率和总生存期。分析循环肿瘤 DNA 以确定卡马替尼耐药机制。
结果
2016 年 5 月至 2019 年 11 月期间共入组 20 例患者，包括 15 例 MET 跳跃改变患者和 5 例 MET 扩增患者。所有患者均接受过克唑替尼治疗；3 例患者还接受过其他 MET 靶向治疗。克唑替尼与卡马替尼之间的中位间隔为 22 天（范围：4-374 天）。2 例（10%）患者对卡马替尼有客观缓解，14 例患者疾病稳定，疾病控制率（DCR）为 80%。在因不耐受而停用克唑替尼的 5 例患者中，DCR 为 83%，其中 2 例患者肿瘤缩小最明显，分别为-25%和-28%。4 例有可测量脑转移的患者颅内疾病控制率为 100%，未观察到颅内客观缓解。总体而言，中位无进展生存期和总生存期分别为 5.5 个月（95%置信区间：1.3-11.0）和 11.3 个月（95%置信区间：5.5-未达到）。在克唑替尼后、卡马替尼前的血浆中，反复检测到 MET D1228 和 Y1230 突变以及 MAPK 改变。在卡马替尼进展时，在血浆中检测到新的和持续的 MET 突变和 MAPK 通路改变。
结论
卡马替尼在克唑替尼预处理的 MET 改变的非小细胞肺癌中具有中等活性，可能是由于存在重叠的耐药机制。
Zotero 插件