Entry Detail
| General information | |
| Database: | DB00015 |
| Objective: | Bevacizumab plus fluoropyrimidinebased chemotherapy is standard treatment for firstline and bevacizumabnaive secondline metastatic colorectal cancer. This study assessed continued use of bevacizumab plus standard secondline chemotherapy in patients with metastatic colorectal cancer progressing after standard firstline bevacizumabbased treatment. |
| Authors: | Bennouna J, et al |
| Title: | Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomisedphase 3 trial. |
| Journal: | Lancet Oncol |
| Year: | 2013 |
| PMID: | 23168366 |
| Trial Design | |
| Clinical Trial Id: | NCT00700102 |
| Agent: | bevacizumab |
| Target: | Vascular endothelial growth factor Epidermal growth factor receptor |
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | advanced colorectal cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | bevacizumab+standard secondline chemotherapy |
| Study Type: | an openlabel, phase III randomised study |
| Key Patients Feature: | Pts in 220 centres in Austria, Belgium, Czech Republic, Denmark, Estonia, Finland, France, Germany, the Netherlands, Norway, Portugal, Saudi Arabia, Spain, Stheyden, and Switzerland, (aged more than and equal to 18 years) with unresectable, histologically confirmed metastatic colorectal cancer progressing up to 3 months after discontinuing firstline bevacizumab plus chemotherapy |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | standard secondline chemotherapy alone |
| Treatment Info: | patients were randomly assigned in a 1:1 ratio to secondline chemotherapy with or without bevacizumab 2.5 mg/kg per week equivalent (either 5 mg/kg every 2 weeks or 7.5 mg/kg every 3 weeks, intravenously). The choice between oxaliplatinbased or irinotecanbased secondline chemotherapy depended on the firstline regimen (switch of chemotherapy). A combination of a permuted block design and the Pocock and Simon minimisation algorithm was used for the randomisation. |
| Primary End Point: | overall survival, analysed by intention to treat. |
| Secondary End Point: | NA |
| Patients Number: | 820 |
| Trial Results | |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 5.7 months (95% CI 5.2-6.2) vs 4.1 months (3.7-4.4) (HR 0.68, 95% CI 0.59-0.78; unstratified logrank p<0.0001 |
| Median OS A vs. C: | 11.2 ms (95% CI 10.412.2) vs 9.8 ms (8.910.7) (HR 0.81, 95% CI 0.690.94; unstratified logrank test p=0.0062). |
| Adverse Event(agent arm): | Grade 35 bleeding or haemorrhage (eight [2%] vs one [<1%]), gastrointestinal perforation (seven [2%] vs three [<1%]), and venous thromboembolisms (19 [5%] vs 12 [3%]) were more common in the bevacizumab plus chemotherapy group than in the chemotherapy alone group. The most frequently reported grade 35 adverse events were neutropenia (65 [16%] in the bevacizumab and chemotherapy group vs 52 [13%] in the chemotherapy alone group), diarrhoea (40 [10%] vs 34 [8%], respectively), and asthenia (23 [6%] vs 17 [4%], respectively). Treatmentrelated deaths were reported for four patients in the bevacizumab plus chemotherapy group and three in the chemotherapy alone group. |
| Conclusions: | Maintenance of VEGF inhibition with bevacizumab plus standard secondline chemotherapy beyond disease progression has clinical benefits in patients with metastatic colorectal cancer. This approach is also being investigated in other tumour types, including metastatic breast and non small cell lung cancers. |