Chan Jennifer A, Geyer Susan, Zemla Tyler, Knopp Michael V, Behr Spencer, Pulsipher Sydney, Ou Fang-Shu, Dueck Amylou C, Acoba Jared, Shergill Ardaman, Wolin Edward M, Halfdanarson Thorvardur R, Konda Bhavana, Trikalinos Nikolaos A, Tawfik Bernard, Raj Nitya, Shaheen Shagufta, Vijayvergia Namrata, Dasari Arvind, Strosberg Jonathan R, Kohn Elise C, Kulke Matthew H, O'Reilly Eileen M, Meyerhardt Jeffrey A
Dana-Farber Cancer Institute, Boston.
Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN.
N Engl J Med. 2025 Feb 13;392(7):653-665. doi: 10.1056/NEJMoa2403991. Epub 2024 Sep 16.
Treatment options for patients with advanced neuroendocrine tumors are limited. The efficacy of cabozantinib in the treatment of previously treated, progressive extrapancreatic or pancreatic neuroendocrine tumors is unclear.
We enrolled two independent cohorts of patients - those with extrapancreatic neuroendocrine tumors and those with pancreatic neuroendocrine tumors - who had received peptide receptor radionuclide therapy or targeted therapy or both. Patients were randomly assigned in a 2:1 ratio to receive cabozantinib at a dose of 60 mg daily or placebo. The primary end point was progression-free survival as assessed by blinded independent central review. Key secondary end points included objective response, overall survival, and safety.
In the cohort of 203 patients with extrapancreatic neuroendocrine tumors, the median progression-free survival with cabozantinib was 8.4 months, as compared with 3.9 months with placebo (stratified hazard ratio for progression or death, 0.38; 95% confidence interval [CI], 0.25 to 0.59; P<0.001). In the cohort of 95 patients with pancreatic neuroendocrine tumors, the median progression-free survival with cabozantinib was 13.8 months, as compared with 4.4 months with placebo (stratified hazard ratio, 0.23; 95% CI, 0.12 to 0.42; P<0.001). The incidence of confirmed objective response with cabozantinib was 5% and 19% among patients with extrapancreatic and pancreatic neuroendocrine tumors, respectively, as compared with 0% with placebo. Grade 3 or higher adverse events were noted in 62 to 65% of the patients treated with cabozantinib, as compared with 23 to 27% of the patients who received placebo. Common treatment-related adverse events of grade 3 or higher included hypertension, fatigue, diarrhea, and thromboembolic events.
Cabozantinib, as compared with placebo, significantly improved progression-free survival in patients with previously treated, progressive advanced extrapancreatic or pancreatic neuroendocrine tumors. Adverse events were consistent with the known safety profile of cabozantinib. (Funded by the National Cancer Institute and others; CABINET ClinicalTrials.gov number, NCT03375320.).
晚期神经内分泌肿瘤患者的治疗选择有限。卡博替尼治疗既往接受过治疗且病情进展的胰腺外或胰腺神经内分泌肿瘤的疗效尚不清楚。
我们纳入了两个独立的患者队列——胰腺外神经内分泌肿瘤患者和胰腺神经内分泌肿瘤患者——这些患者接受过肽受体放射性核素治疗或靶向治疗或两者皆接受过。患者按2:1的比例随机分配，接受每日60毫克剂量的卡博替尼或安慰剂。主要终点是由盲法独立中央审查评估的无进展生存期。关键次要终点包括客观缓解、总生存期和安全性。
在203例胰腺外神经内分泌肿瘤患者队列中，卡博替尼组的中位无进展生存期为8.4个月，而安慰剂组为3.9个月（进展或死亡的分层风险比为0.38；95%置信区间[CI]，0.25至0.59；P<0.001）。在95例胰腺神经内分泌肿瘤患者队列中，卡博替尼组的中位无进展生存期为13.8个月，而安慰剂组为4.4个月（分层风险比为0.23；95%CI，0.12至0.42；P<0.001）。卡博替尼组在胰腺外和胰腺神经内分泌肿瘤患者中确认的客观缓解率分别为5%和19%，而安慰剂组为0%。接受卡博替尼治疗的患者中有62%至65%出现3级或更高等级的不良事件，而接受安慰剂治疗的患者中这一比例为23%至27%。常见的3级或更高等级的与治疗相关的不良事件包括高血压、疲劳、腹泻和血栓栓塞事件。
与安慰剂相比，卡博替尼显著改善了既往接受过治疗且病情进展的晚期胰腺外或胰腺神经内分泌肿瘤患者的无进展生存期。不良事件与卡博替尼已知的安全性特征一致。（由美国国立癌症研究所等资助；CABINET ClinicalTrials.gov编号，NCT03375320。）
