A phase II study of bevacizumab and temsirolimus in advanced extra-pancreatic neuroendocrine tumors.

Endocrine-related cancer Pub Date : 2023-09-13 Print Date: 2023-11-01 DOI:10.1530/ERC-22-0301
Sonia M Abuzakhm, Vineeth Sukrithan, Briant Fruth, Rui Qin, Jonathan Strosberg, Timothy J Hobday, Thomas Semrad, Diane Reidy-Lagunes, Hedy Lee Kindler, George P Kim, Jennifer J Knox, Andreas Kaubisch, Miguel Villalona-Calero, Helen Chen, Charles Erlichman, Manisha H Shah
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Abstract

We assessed the efficacy and safety of combining bevacizumab with temsirolimus in patients with advanced extra-pancreatic neuroendocrine tumors. This NCI-sponsored multicenter, open-label, phase II study (NCT01010126) enrolled patients with advanced, recurrent, or metastatic extra-pancreatic neuroendocrine tumors. All patients were treated with temsirolimus and bevacizumab until disease progression or unacceptable toxicity. Temsirolimus 25 mg was administered i.v. on days 1, 8, 15, and 22 and bevacizumab 10 mg/kg i.v. on days 1 and 15 of a 4-week cycle. Discontinuation of temsirolimus or bevacizumab did not require discontinuation of the other agent. The primary endpoints were objective response rate and 6-month progression-free survival rate. Fifty-nine patients were enrolled in this study, and 54 were evaluated for efficacy and adverse events. While median progression-free survival was 7.1 months, the median duration of treatment with temsirolimus was 3.9 months and that with bevacizumab was 3.5 months. The objective response rate of combination therapy was 2%, and 6-month progression-free survival was 48%. The most frequently reported grade 3-4 adverse events included fatigue (13%), hypertension (13%), and bleeding (13%). Close to 54% of the patients discontinued treatment due to adverse events, refusal of further treatment, or treatment delays. Three deaths occurred in the study, of which two were due to treatment-related bowel perforations. Given the minimal efficacy and increased toxicity seen with the combination of bevacizumab and temsirolimus, we do not recommend the use of this regimen in patients with advanced extra-pancreatic neuroendocrine tumors.

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贝伐单抗和替西莫司治疗晚期胰腺外神经内分泌肿瘤的II期研究。
我们评估了贝伐单抗联合替西莫司治疗晚期胰腺外神经内分泌肿瘤患者的疗效和安全性。这项nci赞助的多中心、开放标签、II期研究(NCT01010126)招募了晚期、复发或转移性胰腺外神经内分泌肿瘤患者。所有患者均接受替西莫司和贝伐单抗治疗,直到疾病进展或不可接受的毒性。替西莫司25 mg在第1、8、15和22天静脉注射,贝伐单抗10 mg/kg在4周周期的第1和15天静脉注射。停用替西莫司或贝伐单抗不需要停用另一种药物。主要终点为客观缓解率和6个月无进展生存率。59名患者参加了这项研究,其中54名患者进行了疗效和不良事件评估。中位无进展生存期为7.1个月,替西莫司治疗的中位持续时间为3.9个月,贝伐单抗治疗的中位持续时间为3.5个月。联合治疗的客观有效率为2%,6个月无进展生存率为48%。最常见的3-4级不良事件包括疲劳(13%)、高血压(13%)和出血(13%)。近54%的患者因不良事件、拒绝进一步治疗或治疗延误而停止治疗。研究中发生了3例死亡,其中2例是由于治疗相关的肠穿孔。考虑到贝伐单抗和替西莫司联合使用的最小疗效和增加的毒性,我们不推荐在晚期胰腺外神经内分泌肿瘤患者中使用该方案。
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