| General information |
| Database: | DB00726 |
| Objective: | No established treatment exists for pancreatic neuroendocrine tumor (NET) progression after failure of chemotherapy. Everolimus (RAD001), an oral inhibitor of mammalian target of rapamycin, in combination with octreotide has demonstrated encouraging antitumor activity in patients with NETs. |
| Authors: | Yao JC, et al |
| Title: | Daily oral everolimus activity in patients with metastatic pancreatic neuroendocrine tumors after failure of cytotoxic chemotherapy: a phase II trial. |
| Journal: | J Clin Oncol. |
| Year: | 2010 |
| PMID: | 19933912 |
| Trial Design |
| Clinical Trial Id: | NCT00363051 |
| Agent: | everolimus
|
| Target: | Serine/threonineprotein kinase mTOR
|
| Cancer Type: | pancreatic cancer |
| Cancer Subtype: | advanced pancreatic cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | s an openlabel, phase II, nonrandomized study |
| Key Patients Feature: | Eligible patients had a histologically confirmed, well to moderately differentiated, advanced (unresectable or metastatic) pancreatic NET with progressivedisease documented by RECIST during or after cytotoxic chemotherapy. Eligible patients were 18 years of age, with WHO performance status 2 andadequate bone marrow, hepatic, and renal function. |
| Biomarker: | Chromogranin A(CgA) and neuronspecific enolase (NSE) were assessed monthly if elevated at baseline. |
| Biomark Analysis: | Patients with an early CgA or NSE response had a longer PFS compared with patients without an early response. Coadministration of octreotide LAR and everolimus did not impact exposure to either drug. |
| Control Group Info: | stratum 1: everolimus 10 mg/d, n = 115; stratum 2: everolimus 10 mg/d plus octreotide longacting release [LAR], n = 45 |
| Treatment Info: | Patients were stratified by prior octreotide therapy (stratum 1: everolimus 10 mg/d, n 115; stratum 2:everolimus 10 mg/d plus octreotide longacting release [LAR], n=45). Tumor assessments were performed every 3 months. |
| Primary End Point: | objective response rate(ORR)in stratum 1 |
| Secondary End Point: | ORR and PFS, duration of response, OS, safety, and pharmacokinetics. Exploratory objectives included evaluation of biomarkers. |
| Patients Number: | 160 |
| Trial Results |
| DLT_MTD: | Most adverse events (AEs)were mild to moderate in severity. The most common AEs suspectedto be related to study drug in strata 1 and 2 were stomatitis, rash diarrhea, fatigue, and nausea |
| Objective Response Rate: | In stratum 1, ORR by central radiology review was 9.6% (11 of115 patients; 95% CI, 4.9% to 16.5%; Fig 1). The median duration ofresponse was 10.6 months (95% CI, 9.8 months to not available [NA]). Stable disease (SD) was noted in an additional 78 patients(67.8%). Sixteen patients (13.9%) had disease progression as bestoverall response (Table 2). By investigator assessment, ORR was10.4% (95% CI, 5.5% to 17.5%). SD was noted in an additional 71patients (61.7%), and median duration of response was 19.2 months |
| Disease Control Rate: | Stratum 1: 77.4%; Stratum 2: 84.4% |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Median PFS by central radiology review in stratum 1 was 9.7 months (95% CI, 8.3 to 13.3 months); in stratum 2, the median PFS was 16.7 months (95% CI, 11.1 months to NA). By investigator review, median PFS was 8.5 months (95% CI, 7.8 to 11.8 months) in stratum 1 and 15.2 months (95% CI, 9.3 months to NA) in stratum 2. |
| Median OS A vs. C: | Median OS in stratum 1 was 24.9 months (95% CI, 20.2 to 27.1 months). Median OS had not been reached for stratum2 at the timeof data cutoff; the 24month survival rate for stratum2was54.7% (95% CI, 21.7% to 87.8%;). |
| Adverse Event(agent arm): | NA |
| Conclusions: | Daily everolimus, with or without concomitant octreotide LAR, demonstrates antitumor activity as measured by objective response rate and PFS and is well tolerated in patients with advanced pancreatic NETs after failure of prior systemic chemotherapy. |