| General information |
| Database: | DB00990 |
| Objective: | Cetuximab improves survival in patients with Kras wildtype advanced colorectal cancer. they examined the predictive and prognostic significance of additional biomarkers in this setting, in particular BRAF, PIK3CA, and PTEN. |
| Authors: | Karapetis CS, et al |
| Title: | PIK3CA, BRAF, and PTEN status and benefit from cetuximab in the treatment of advanced colorectal cancerresults from NCIC CTG/AGITG CO.17. |
| Journal: | Clin Cancer Res. |
| Year: | 2014 |
| PMID: | 24218517 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | advanced colorectal cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | results from NCIC CTG/AGITG CO.I7 |
| Key Patients Feature: | Available colorectal tumor samples |
| Biomarker: | PTEN expression |
| Biomark Analysis: | None of BRAF, PIK3CA, or PTEN was prognostic for overall or progression free survival in the BSC arm. None was predictive of benefit from cetuximab, either in the whole study population or the Kras wildtype subset. In the Kras wildtype subgroup, the overall survival adjusted HR according to BRAF mutation status was 1.39 (interaction P = 0.69), PIK3CA mutation status HR = 0.79 (interaction P = 0.63), and PTEN expression HR = 0.75 (interaction P = 0.61). |
| Control Group Info: | cetuximab versus best supportive care |
| Treatment Info: | Available colorectal tumor samples were analyzed from the CO.17 study. BRAF mutations were identified in tumorderived DNA by direct sequencing and PIK3CA mutations were identified using a highresolution melting screen with confirmation by sequencing. |
| Primary End Point: | biomarker analysis |
| Secondary End Point: | NA |
| Patients Number: | 572 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | no tumor responses to cetuximab in the 4 patients with BRAF mutant versus 14% (14/101) in patients with BRAF wildtype status. cetuximab was 20% versus 12% in patients with PIK3CA mutant versus wildtype status, respectively. cetuximab was 21% versus 15% in patients with PTEN positive versus negative staining. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | Among BRAF wildtype patients, median OS was 9.7 versus 5.0 months for cetuximab versus BSC, respectively (HR = 0.52; P < 0.0001). Among patients with tumor that harbored BRAF mutations, the median OS was 1.77 versus 2.97 months for cetuximab versus BSC (HR = 0.84; P = 0.81) and PFS HR was 0.76 (P = 0.69). Among PIK3CA wild type, median OS was 9.5 versus 5.1 months for cetuximab versus BSC, respectively (HR = 0.53; P = 0.0002). Among PIK3CA mutant, median OS was 9.9 versus 3.6 months for cetuximab versus BSC, respectively (HR = 0.43; P = 0.059). Among PTEN positive, the median OS was 9.9 versus 5.4 months for cetuximab versus BSC, respectively (HR = 0.66; P = 0.32). Among PTEN negative, median OS was 9.1 versus 5.1 months for cetuximab versus BSC (HR = 0.63; P = 0.065) |
| Adverse Event(agent arm): | NA |
| Conclusions: | In chemotherapyrefractory colorectal cancer, neither PIK3CA mutation status nor PTEN expression were prognostic, nor were they predictive of benefit from cetuximab. Evaluation of predictive significance of BRAF mutations requires a larger sample size. |