| General information |
| Database: | DB00728 |
| Objective: | Treatment with gemcitabine provides modest benefits in patients with metastatic pancreatic cancer. The addition of erlotinib to gemcitabine shows a small but significant improvement in overall survival (OS) versus gemcitabine alone.phase II results for bevacizumab plus gemcitabine provided the rationale for a phase III trial of gemcitabineerlotinib plus bevacizumab or placebo. |
| Authors: | Van Cutsem E, et al |
| Title: | Phase III trial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. |
| Journal: | J Clin Oncol. |
| Year: | 2009 |
| PMID: | 19307500 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | pancreatic cancer |
| Cancer Subtype: | advanced pancreatic cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 13 |
| Therapeutic Combination Content: | bevacizumab + gemcitabine and erlotinib |
| Study Type: | multicenter randomized, phaseIII trial |
| Key Patients Feature: | patients aged 18 years with histologically or cytologicallydocumented metastatic adenocarcinoma of the pancreas. Patients with unresectable locally advanced disease without evidence of metastases elsewherewere not eligible. For inclusion in the study, patients were required to haveKarnofsky performance status (KPS) 60%; adequate blood counts and liverand kidney function; proteinuria dipstick less than 2 ( 1 g in 24hour urinecollection if proteinuria dipstick 2 ). |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | bevacizumab VS placebo |
| Treatment Info: | patients were randomly assigned to receive gemcitabine (1, 000 mg/m(2)/week), erlotinib (100 mg/day), and bevacizumab (5 mg/kg every 2 weeks) or gemcitabine, erlotinib, and placebo in this doubleblind, phase III trial. |
| Primary End Point: | OS |
| Secondary End Point: | progression free survival (PFS), disease control rate, and safety |
| Patients Number: | 607 |
| Trial Results |
| DLT_MTD: | Grade 3 to 5 events were observedin 220 patients (74%) in the bevacizumab arm and in 202patients (70%) in the placebo arm. |
| Objective Response Rate: | Median OS was 7.1 and 6.0 months in the bevacizumab and placebo arms, respectively(hazard ratio [HR], 0.89; 95% CI, 0.74 to 1.07; P .2087Adding bevacizumab to gemcitabineerlotinib significantly improved PFS (HR, 0.73;95% CI, 0.61 to 0.86; P .0002) |
| Disease Control Rate: | 62.1% in the bevacizumab arm and 58.5% in the placebo arm (P= .3621). |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 4.6 months versus 3.6 months for bevacizumab and placebo |
| Median OS A vs. C: | 7.1 and 6.0 months in the bevacizumab and placebo arms, respectively (hazard ratio [HR], 0.89; 95% CI, 0.74 to 1.07; P = .2087) |
| Adverse Event(agent arm): | Grade 3 to 5 events were observed in 220 patients (74%) in the bevacizumab arm and in 202 patients (70%) in the placebo arm. Treatment with bevacizumab plus gemcitabineerlotinib was well tolerated: safety data did not differ from previously described safety profiles for individual drugs. |
| Conclusions: | The primary objective was not met. The addition of bevacizumab to gemcitabineerlotinib did not lead to a statistically significant improvement in OS in patients with metastatic pancreatic cancer. PFS, hotheyver, was significantly longer in the bevacizumab group compared with placebo. No unexpected safety events they were observed from adding bevacizumab to gemcitabineerlotinib. |