Entry Detail
| General information | |
| Database: | DB00724 |
| Objective: | The multitargeted tyrosine kinase inhibitor sunitinib has shown activity against pancreatic neuroendocrine tumors in preclinical models andphase 1 and 2 trials. |
| Authors: | Raymond E, et al |
| Title: | Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. |
| Journal: | N Engl J Med. |
| Year: | 2011 |
| PMID: | 21306237 |
| Trial Design | |
| Clinical Trial Id: | NCT00428597 |
| Agent: | sunitinib |
| Target: | FL cytokine receptor Mast/stem cell growth factor receptor Vascular endothelial growth factor receptor 2 Plateletderived growth factor receptor |
| Cancer Type: | pancreatic cancer |
| Cancer Subtype: | Pancreatic Neuroendocrine Tumors |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a multinational, randomized, doubleblind, placebocontrolledphaseIII trial |
| Key Patients Feature: | Eligible patients had pathologically confirmed, welldifferentiated pancreatic endocrine tumorsthat were advanced, metastatic, or both, 25, 26 andwere not candidates for surgery. Additionalinclusion criteria were the following: documenteddisease progression within the previous 12 monthsas assessed according to the Response EvaluationCriteria in Solid Tumors (RECIST27); one or moremeasurable target lesions; an Eastern Cooperative Oncology Group performance status of 0 or1 (with 0 indicating that the patient is fully activeand 1 that the patient is restricted in physicallystrenuous activity but ambulatory and able to carry out work of a light or sedentary nature [e.g., light housework or office work]); and adequatehematologic, hepatic, and renal function. TheKi67 index (the percentage of cells that were positive for Ki67, determined by immunostaining ofthe primary tumor) was assessed at screeningfrom available pathology reports. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | sunitinib VS placebo |
| Treatment Info: | A total of 171 patients were randomly assigned (in a 1:1 ratio) to receive best supportive care with either sunitinib at a dose of 37.5 mg per day or placebo. |
| Primary End Point: | progression free survival |
| Secondary End Point: | objective response rate, overall survival, and safety |
| Patients Number: | 171 |
| Trial Results | |
| DLT_MTD: | The majority of adverse events in both groupswere grade 1 or 2 in severity, with grade 3 or 4 events more common in patients who receivedsunitinib (Table 3). The most common adverseevents associated with sunitinib were diarrhea, nausea, asthenia, vomiting, and fatigue |
| Objective Response Rate: | Eight patients who received sunitinib had a confirmedtumor response (two had complete responsesand six had partial responses) (Fig. 1C);the objective response rate was 9.3% (95% CI, 3.2to 15.4). No objective responses were observedwith placebo (Fig. 1C) (P = 0.007 for the between group difference) |
| Disease Control Rate: | NA |
| Median Time to Progression: | 3.1 months (range, 0.8 to 11.1). |
| Median PFS A vs. C: | 11.4 months in the sunitinib group as compared with 5.5 months in the placebo group (hazard ratio for progression or death, 0.42; 95% confidence interval [CI], 0.26 to 0.66; P<0.001). |
| Median OS A vs. C: | NR(not reached) |
| Adverse Event(agent arm): | At the data cutoff point, 9 deaths were reported in the sunitinib group (10%) versus 21 deaths in the placebo group (25%) (hazard ratio for death, 0.41; 95% CI, 0.19 to 0.89; P = 0.02). The most frequent adverse events in the sunitinib group were diarrhea, nausea, vomiting, asthenia, and fatigue. |
| Conclusions: | Continuous daily administration of sunitinib at a dose of 37.5 mg improved progression free survival, overall survival, and the objective response rate as compared with placebo among patients with advanced pancreatic neuroendocrine tumors. |