Cetuximab Is a Good Option When Standard Treatment Fails, Large Trial Reports

LOS ANGELES-In patients who have exhausted all other treatment options for metastatic colorectal cancer, cetuximab(Drug information on cetuximab) (Erbitux) is well tolerated and active. This is the conclusion drawn from one of the largest trials to date of single-agent monoclonal antibody therapy in chemotherapy-refractory metastatic colorectal cancer (abstract 3510). A response rate of about 12% was reported for cetuximab initiated in nearly 350 patients in whom regimens with irinotecan(Drug information on irinotecan) (CPT-11, Camptosar) and with oxaliplatin(Drug information on oxaliplatin) (Eloxatin) had failed. Median survival time approached 7 months (abstract 3510). The study report, "demonstrates convincingly that this agent has activity in heavily pretreated patients and is well tolerated," reported Heinz-Josef Lenz, MD, director of gastrointestinal oncology at USC/Norris Comprehensive Cancer Center, Los Angeles. "A response rate of over 10% is impressive: compare to that the response rates with FOLFOX [fluorouracil (5-FU)/folinic acid/oxaliplatin] and FOLFIRI [5-FU/folinic acid/irinotecan] in second-line chemotherapy," Dr. Lenz stated. Interestingly, response was con- firmed in one of nine patients whose tumors had stained negative for epidermal growth factor receptor (EGFR). This was notable because the activity of cetuximab is thought to be related to its activity against EGFR. As a result of this finding, which included one confirmed and one unconfirmed response, investigators launched a new trial to evaluate the efficacy of cetuximab in EGFR-negative tumors. Impressive Response Rate
For the study, a total of 346 patients with metastatic colorectal cancer received cetuximab at an initial dose of 400 mg/m², followed by weekly treatments at a dose of 250 mg/m². The patients had undergone a median of four prior regimens containing irinotecan or oxaliplatin. All but nine patients had tumors with immunohistochemical evidence of EGFR expression. The objective response rate was 12.1% (42 patients, all partial responses) by investigator assessment and 11.6% (40 patients) by independent review committee (IRC) assessment (see Table 1). Another 31.8% (110 patients) had stable disease by IRC assessment. The median overall survival time was 6.7 months. These results were consistent with prior studies of cetuximab monotherapy in metastatic colorectal cancer, according to the investigators. Safe, Well Tolerated
The most adverse event was an acneiform rash characteristic of treatment with an EGFR-targeted agent. The rash was seen in 90% of patients treated, but in only 12% of cases was the rash grade 3/4 in severity, including 2% grade 4. Infusion reactions, almost all grade 1/2, were noted in 17% of patients. Other reported adverse events included diarrhea, fatigue or malaise, nausea and vomiting, and mucositis/stomatitis. "This is an effective agent in refractory patients, and it is safe and well tolerated," Dr. Lenz said. Further investigation is warranted in "EGFR nondetectable" tumors, investigators added. Of the nine patients with tumors in which EGFR could not be detected, four had disease control, including the one confirmed response and three patients rated as having stable disease. In addition, eight of the nine patients had the characteristic acneiform rash.