American Society of Clinical Oncology

Posted by James

Cetuximab (Erbitux)

The epidermal growth factor receptor (EGFR) is expressed by most colorectal cancers. Cetuximab (Erbitux, Bristol-Myers Squib) is an immunoglobulin (IgG1) monoclonal antibody that specifically targets EGFR with high affinity. Dr. Van Cutsem presented results of the CRYSTAL trial (Cetuximab Combined with Irinotecan in First-Line Therapy for Metastatic Colo-rectal Cancer). This is the first phase 3 study to assess the combination of cetuximab plus FOLFIRI as a first-line therapy for colorectal cancer. FOLFIRI consists offormic acid (leucovorin), 5-/luorouracil (5-FU), and irinotecan (Camptosar, Pfizer).

CRYSTAL included 1,217 patients (mean age, 61 years) with histologically confirmed unresectable metastatic colorectal cancer with EGFR expression in either the primary tumor or in metastases. Patients were chemotherapy-naive or had stopped adjuvant therapy, excluding irinotecan, at least six months previously. They were randomly assigned to receive cetuximab plus FOLFIRI or FOLFIRI alone. The trial’s primary endpoint was progression-free survival. canadian pharmacy cialis

Reporting efficacy results, Dr. Van Cutsem said that CRYSTAL met its primary endpoint. For the cetuximab/FOLFIRI arm, progression-free survival was 8.9 months; for the FOLFIRI-alone arm, the rate was 8 months (15% reduction, hazard ratio [HR, 0.851; P = 0.0479). At one year, progression-free survival rates were 34% with cetuximab/FOLFIRI and 23% for FOLFIRI alone.

The overall response rate was higher for the combination arm (46.9%) than with the FOLFIRI-alone arm (38.7°%), and the disease control rate was similar for both groups (about 85%).

Significantly more cetuximab/FOLFIRI patients (6%) were able to have surgery with curative intent, compared with the FOLFIRI-alone group (2.5%). More patients receiving the combination (4.3%) had no residual tumor after resection, compared with 1.5% receiving FOLFIRI alone. More patients with metastases only to the liver had no residual tumor (9.8% receiving cetuximab/FOLFIRI vs. 4.5% receiving only FOLFIRI).

Treatment discontinuation rates were slightly higher with FOLFIRI alone (86 patients) than with the combination (81 patients). Grade 3 and 4 adverse events, however, occurred more often with cetuximab/FOLFIRI (78%) than with FOLFIRI alone (59.5%). Rates of neutropenia (26.7% with the combinaion vs. 23.3% with FOLFIRI only) and of febrile neutropenia (2.7% with the combination vs. 2.2%) were generally similar. Skin reactions were higher with the cetuximab/FOLFIRI regimen (18.7%) than with FOLFIRI (0.2%), and these rates strongly correlated with efficacy. None of the patients had grade 4 lesions, and there were no cetuximab-related deaths. prescription drugs online pharmacy

Dr. Van Cutsem concluded that the CRYSTAL trial met its primary objective of demonstrating that adding cetuximab to FOLFIRI increased progression-free survival.