| General information |
| Database: | DB00309 |
| Objective: | ML18147 evaluated continued bevacizumab with secondline chemotherapy for patients with metastatic colorectal cancer (mCRC) progressing after the standard firstline bevacizumabcontaining therapy. |
| Authors: | Kubicka S, et al |
| Title: | Multicenterphase I trial of the mitogenactivated protein kinase 1/2 inhibitor BAY 869766 in patients with advanced cancer. |
| Journal: | Ann Oncol. |
| Year: | 2013 |
| PMID: | 23852309 |
| Trial Design |
| Clinical Trial Id: | NCT00700102 |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | advanced colorectal cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | Bevacizumab+ chemotherapy |
| Study Type: | a prospective, multicenter, intergroup, randomized, openlabel, phase III study |
| Key Patients Feature: | patients with metastatic colorectal cancer (mCRC) progressing after the standard firstline bevacizumabcontaining therapy |
| Biomarker: | tumor KRAS and Btype Raf kinase (BRAF) mutational status |
| Biomark Analysis: | In both analyses, no treatment interaction by KRAS status was observed (PFS, P = 0.4436; OS, P = 0.1266). |
| Control Group Info: | single arm |
| Treatment Info: | Evaluating outcomes according to tumor Kirsten rat sarcoma virus oncogene (KRAS) status was an exploratory analysis. KRAS data were collected from local laboratories (using their established methods) and/or from a central laboratory (mutationspecific Scorpion amplificationrefractory mutation system). |
| Primary End Point: | Exploratory end points in ML18147 included analysis of tumor KRAS and Btype Raf kinase (BRAF) mutational status. |
| 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: | 6.4 months for bevacizumab plus chemotherapy and 4.5 months for chemotherapy [P < 0.0001; HR = 0.61; 95% confidence interval (CI): 0.490.77] for wildtype KRAS and 5.5 and 4.1 months, respectively (P = 0.0027; HR = 0.70; 95% CI: 0.560.89) for mutant KRAS. |
| Median OS A vs. C: | 15.4 and 11.1 months, respectively (P = 0.0052; HR = 0.69; 95% CI: 0.530.90) for wildtype KRAS and 10.4 versus 10.0 months, respectively (P = 0.4969; HR = 0.92; 95% CI: 0.711.18) for mutant KRAS. |
| Adverse Event(agent arm): | NA |
| Conclusions: | Bevacizumab beyond first progression represents an option for patients with mCRC treated with bevacizumab plus standard firstline chemotherapy, independent of KRAS status. |