| General information |
| Database: | DB00733 |
| Objective: | This multicenter study evaluated the antitumor activity of cetuximab, an immunoglobulin G1 antibody directed at the epidermal growth factor receptor (EGFR), in metastatic colorectal carcinoma (CRC) refractory to irinotecan, oxaliplatin, and a fluoropyrimidine. It also evaluated the safety, pharmacokinetics, immunokinetics, and biologic determinants of activity. |
| Authors: | Lenz HJ, et al |
| Title: | Multicenterphase II and translational study of cetuximab in metastatic colorectal carcinoma refractory to irinotecan, oxaliplatin, and fluoropyrimidines. |
| Journal: | J Clin Oncol. |
| Year: | 2006 |
| PMID: | 17050875 |
| 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: | Multicenterphase II and Translational Study |
| Key Patients Feature: | Patients with pathologically confirmed CRC and any degree of EGFRimmunostaining as performed at Impath (Los Angeles, CA) were eligible.EGFR progression must have been documented during or within 3 monthsafter treatment with irinotecan, oxaliplatin, and fluoropyrimidines in themetastatic setting or within 6 months of adjuvant therapy, with at least twochemotherapy regimens for metastatic disease or adjuvant therapy plus at leastone regimen for metastatic disease. The extent of prior chemotherapy was notrestricted.Eligibilitycriteriaalsoincluded:age 18years, EasternCooperativeOncology Group performance status of 0 or 1; life expectancy of at least 3months; no major surgery, radiation, chemotherapy, or investigational agentwithin 4 weeks; normal hematopoietic, hepatic, and renal functions; measurable disease; no coexisting medical problem of sufficient severity to limit studycompliance; no history of brain metastases; and no prior treatment withEGFRtargetingagentsormurineorchimericantibodies. |
| Biomarker: | EGFR gene sequencing of the tyrosine kinase domain and gene copy number assessments were performed. |
| Biomark Analysis: | In contrast, clinical benefit did not relate to EGFR immunostaining. EGFR tyrosine kinase domain mutations were not identified, and EGFR gene copy number did not relate to response or PFS, but to survival (P = .03). |
| Control Group Info: | single arm |
| Treatment Info: | pts were treated with cetuximab at a loading dose of 400 mg/m2 follotheyd by 250 mg/m2 weekly. |
| Primary End Point: | toxicity, safety, and pharmacokinetics; to relate EGFR gene mutations and gene amplification to therapeutic results |
| Secondary End Point: | NA |
| Patients Number: | 346 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | The response rates in 346 patients, as determined by the investigators and IRC, were 12.4% (95%CI, 9.1 to 16.4) and 11.6% (95% CI, 8.4 to 16.4). The median progression free survival (PFS) andsurvival times were 1.4 months (95% CI, 1.4 to 2.1) and 6.6 months (95% CI, 5.6 to 7.6), respectively |
| Disease Control Rate: | 0.434 |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 1.4 months (95% CI, 1.4 to 2.1) |
| Median OS A vs. C: | 6.6 months (95% CI, 5.6 to 7.6) |
| Adverse Event(agent arm): | An acneiform rash occurred in 82.9% of patients; grade 3 rash was observed in 4.9%. Response and survival related strongly to the severity of the rash. In contrast, clinical benefit did not relate to EGFR immunostaining. |
| Conclusions: | Cetuximab is active and well tolerated in metastatic CRC refractory to irinotecan, oxaliplatin, and fluoropyrimidines. The severity of rash was related to efficacy. Neither EGFR kinase domain mutations nor EGFR gene amplification appear to be essential for response to cetuximab in this setting. |