编者按：2024年欧洲肿瘤内科学会（ESMO）大会（9月13~17日，巴塞罗那）上展示的CABINET研究（摘要号11410）更新了卡博替尼对比安慰剂治疗既往治疗后进展后的晚期神经内分泌肿瘤 （NET）的最新结果。在会议现场，我们特邀主要研究者、波士顿Dana-Farber癌症研究所的Jennifer Chan教授在现场接受了我们的专访。

研究概况

1141O - Cabozantinib versus placebo for advanced neuroendocrine tumors (NET) after progression on prior therapy (CABINET Trial/Alliance A021602): Updated results including progression free-survival (PFS) by blinded independent central review (BICR) and subgroup analyses

卡博替尼对比安慰剂治疗既往治疗后进展后的晚期神经内分泌肿瘤 （NET）（CABINET 试验/Alliance A021602）的更新结果：包括盲法独立中心评论 （BICR） 的PFS和亚组分析

背景

方法

局部晚期或转移性非胰腺NET（epNET）或胰腺NET（pNET）患者以2∶1的比例随机分配，接受CABO 60 mg/d vs PB。入组条件包括注册前12个月内RECIST评估的疾病进展，≥1次既往治疗。预先指定的主要终点：BICR评估的PFS。次要终点：ORR、总生存期（OS）、安全性（图1）。

图1.研究设计

结果

图2. CABO显著改善了两组患者中经BICR评估的PFS

图3. 患者主要的安全性事件

结论

研究者说

Dr Chan: Thanks for having me. I am Jennifer Chan. I am a medical oncologist in Boston at the Dana-Farber Cancer Institute. At ESMO 2024, I had the pleasure of presenting the updated results from the CABINET trial. This was a randomized phase III study of cabozantinib versus placebo for patients with advanced neuroendocrine tumors whose disease had progressed after prior therapy. The main rationale for doing this study was that we really do need newer and more effective treatment options for patients with neuroendocrine tumors. We also know that angiogenesis inhibitors, agents that inhibit the VEGF pathway, are active for treating neuroendocrine tumors, and that inhibition of MET can also impede the resistance that develops. We had done a phase II trial that showed promising activity with cabozantinib, and we have studied that further in the CABINET trial. This trial had two cohorts of patients. There was one with extra-pancreatic neuroendocrine tumors, and one with pancreatic neuroendocrine tumors. They all had had at least one prior therapy for their disease. In the extra-pancreatic neuroendocrine tumors, we studied a very broad range of patients with primary tumor sites that, for instance, started in the GI tract or the lung, all grades of disease, irrespective also of tumor functional status. In the trial, we did a randomization 2:1 to cabozantinib or placebo, and patients continued treatment until disease progression or until they had to stop for other reasons. The primary endpoint was progression-free survival. What we observed in the extra-pancreatic neuroendocrine tumor cohort was that there was a significant improvement in progression-free survival in patients receiving cabozantinib. The specific hazard ratio for progression-free survival in this cohort was 0.38, so there was a 62% reduction in the risk for disease progression or death for these patients. In the pancreatic neuroendocrine tumor cohort,  we similarly found improvement in progression-free survival for patients receiving cabozantinib. The hazard ratio for progression-free survival in this cohort was 0.23, translating into a 77% reduction in the risk of disease progression or death in the patients treated with cabozantinib. We also looked at the safety profile, and we found that the adverse events were consistent with what we have seen with cabozantinib in other settings. For instance, the most common adverse events included transaminitis, there was fatigue, there was hypertension and diarrhea. These are known side effects of cabozantinib. Patients were able to be dose-reduced to manage the side effects of treatment. But we didn’t observe any new safety signals. Based on the data we observed, we are hopeful this will be a new treatment option for patients. Again, thinking about our patients, we really want to have as many options as we can to help treat their disease.