| General information |
| Database: | DB00664 |
| Objective: | There are few effective therapies for pancreatic neuroendocrine tumors (PNETs). Recent placebocontrolledphase III trials of the mammalian target of rapamycin (mTOR) inhibitor everolimus and the vascular endothelial growth factor (VEGF)/plateletderived growth factor receptor inhibitor sunitinib have noted improved progression free survival (PFS). Preclinical studies have suggested enhanced antitumor effects with combined mTOR and VEGF pathwaytargeted therapy. They conducted a clinical trial to evaluate combination therapy against these targets in PNETs. |
| Authors: | Hobday TJ, et al |
| Title: | Multicenterphase II Trial of Temsirolimus and Bevacizumab in Pancreatic Neuroendocrine Tumors. |
| Journal: | J Clin Oncol. |
| Year: | 2015 |
| PMID: | 25488966 |
| Trial Design |
| Clinical Trial Id: | NCT01010126 |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | pancreatic cancer |
| Cancer Subtype: | advanced pancreatic neuroendocrine tumor |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Temsirolimus+ Bevacizumab |
| Study Type: | a multicenter, singlearm, openlabelphase II trial |
| Key Patients Feature: | Eligible patients had histologically confirmed locally advanced or metastatic, wellormoderatelydifferentiatedNETswithclearevidenceofpancreaticorigin, were age 18 years, and had an Eastern Cooperative Oncology Groupperformancestatusof0to1.EvidenceofprogressivediseaseasdocumentedbyRECIST (version 1.1) within 7 months before study entry was required. Thiswas to approximate the eligibility criterion of progressive disease within 6months used in prior trials by this group and others but to allow 7 months tomaximize accrual in patients with a rare disease and frequently used followupintervals of roughly 3 to 6 months. Adequate organ function, urinalysis with 2 protein, fasting serum cholesterol 350 mg/dL, and triglycerides 1.5 upper limit of normal were required. Patients who had received prior anthracycline chemotherapy were required to have normal left ventricular ejectionfraction before registration. Submission of archived tumor, blood, and serumfor translational studies was required. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | a phase II trial of the mTOR inhibitor temsirolimus 25 mg intravenously (IV) once per week and the VEGFA monoclonal antibody bevacizumab 10 mg/kg IV once every 2 weeks in patients with well or moderately differentiated PNETs and progressive disease by RECIST within 7 months of study entry. |
| Primary End Point: | tumor response rate and 6month PFS |
| Secondary End Point: | NA |
| Patients Number: | 58 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Confirmed response rate (RR) was 41% (23 of 56 patients). |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 13.2 months (95% CI, 11.2 to 16.6) |
| Median OS A vs. C: | 34 months (95% CI, 27.1 to not reached). |
| Adverse Event(agent arm): | For evaluable patients, the most common grade 3 to 4 adverse events attributed to therapy were hypertension (21%), fatigue (16%), lymphopenia (14%), and hyperglycemia (14%). |
| Conclusions: | The combination of temsirolimus and bevacizumab had substantial activity and reasonable tolerability in a multicenterphase II trial, with RR of 41%, well in excess of single targeted agents in patients with progressive PNETs. Sixmonth PFS was a notable 79% in a population of patients with disease progression by RECIST criteria within 7 months of study entry. On the basis of this trial, continued evaluation of combination mTOR and VEGF pathway inhibitors is warranted. |