| General information |
| Database: | DB00033 |
| Objective: | Panitumumab, a fully human antibody against the epidermal growth factor receptor (EGFR), has activity in a subset of patients with metastatic colorectal cancer (mCRC). Although activating mutations in KRAS, a small Gprotein downstream of EGFR, correlate with poor response to antiEGFR antibodies in mCRC, their role as a selection marker has not been established in randomized trials. |
| Authors: | Amado RG, et al |
| Title: | Wildtype KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. |
| Journal: | J Clin Oncol |
| Year: | 2008 |
| PMID: | 18316791 |
| Trial Design |
| Clinical Trial Id: | numbers for studies 20020408 and 20030194 are NCT00113763 and NCT00113776 |
| Agent: | panitumumab
|
| 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: | a phase III mCRC trial |
| Key Patients Feature: | patients with metastatic colorectal cancer |
| Biomarker: | KRAS mutation status; |
| Biomark Analysis: | KRAS mutations were found in 43% of patients. |
| Control Group Info: | best supportive care |
| Treatment Info: | KRAS mutations were detected using polymerase chain reaction on DNA from tumor sections collected in a phase III mCRC trial comparing panitumumab monotherapy to best supportive care |
| Primary End Point: | progression free survival (PFS) differed by KRAS status. |
| Secondary End Point: | NA |
| Patients Number: | 427 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Response rates to panitumumab were 17% and 0%, for the WT and mutant groups, respectively. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | The treatment effect on PFS in the wildtype (WT) KRAS group (hazard ratio [HR], 0.45; 95% CI: 0.34 to 0.59) was significantly greater (P < .0001) than in the mutant group (HR, 0.99; 95% CI, 0.73 to 1.36). Median PFS in the WT KRAS group was 12.3 weeks for panitumumab and 7.3 weeks for BSC. |
| Median OS A vs. C: | WT KRAS patients had longer overall survival (HR, 0.67; 95% CI, 0.55 to 0.82; treatment arms combined). Consistent with longer exposure, more grade III treatmentrelated toxicities occurred in the WT KRAS group |
| Adverse Event(agent arm): | No significant differences in toxicity were observed between the WT KRAS group and the overall population. |
| Conclusions: | Panitumumab monotherapy efficacy in mCRC is confined to patients with WT KRAS tumors. KRAS status should be considered in selecting patients with mCRC as candidates for panitumumab monotherapy. |