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Patients with metastatic colorectal cancer respond better to FOLFOX4 as first-line treatment when the regimen is supplemented with the monoclonal antibody cetuximab, according to the results of a phase II superiority trial.
Overall and progression-free survival data are not yet available from the 337-patient Oxaliplatin and Cetuximab in First-Line Treatment of Metastatic Colorectal Cancer (OPUS) study, headed by Dr. Carsten Bokemeyer of University Hospital in Hamburg, Germany. Data presented in a poster suggest adding cetuximab (Erbitux) to the FOLFOX4 combination of 5-flourouracil (5-FU), leucovorin (FA), and oxaliplatin (Eloxatin) can raise the response rate by 10% in this patient population.
The best overall confirmed response was 46% of patients given cetuximab and FOLFOX4 vs. 36% of those treated with FOLFOX4 alone (P = .064). Statistical significance was achieved among patients with Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Their response rates were 49% and 37%, respectively (P = .032).
Conducted at 70 European centers, the OPUS study included patients with previously untreated metastatic colorectal cancer that expressed the epidermal growth factor receptor (EGFR) and had cancers that were not resectable with curative intent.
The median age of the population was 61 (24-82) years, 181 patients were men, and 305 (91%) had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Randomization assigned 169 patients to the cetuximab-FOLFOX4 regimen: 400 mg/m² initial intravenous infusion of cetuximab on day 1 followed by 250 mg/m² weekly of cetuximab plus FOLFOX4 (85 mg/m² of oxaliplatin plus 5-FU/FA) every 2 weeks. The remaining 168 patients received FOLFOX4 monotherapy every 2 weeks.
Neutropenia, diarrhea, and leukopenia occurred at equal frequencies in both arms. Only grade 1, 2, and 3 skin rash was significantly more frequent with the cetuximab arm, occurring in 9% of patients on the EGFR inhibitor but in none of the patients who were in the control group.
Dr. Bokemeyer and associates concluded that "there was an approximately 50% higher chance of achieving a complete or partial response for those patients receiving cetuximab plus FOLFOX4."
Among the 305 patients with baseline ECOG performance status of 0-1, half responded to the combination therapy, compared with 37% of those on FOLFOX monotherapy (P = .032).
The difference in response rates for the entire cohort fell short of statistical significance but showed a strong trend favoring the addition of cetuximab (46% vs. 36%).
"Analysis of prognostic factors for response uniformly showed an increased chance of a response by 50%-100% in most subgroups with cetuximab plus FOLFOX4 compared to FOLFOX alone," they said, adding that the combination therapy was generally well tolerated.
These results support those of the smaller phase II Acrobat study presented in 2005, said poster discussant Dr. Richard Goldberg.
That study of cetuximab plus FOLFOX4 in 45 patients with metastatic colorectal cancer showed a response rate of 79% based on an independent expert review.
"The study by Dr. Bokemeyer and his colleagues is a larger, multicenter trial and is likely more reliable," according to Dr. Goldberg, a professor of medicine at the University of North Carolina in Chapel Hill.
Bokemeyer C. et al. Cetuximab plus 5-FU/FA/oxaliplatin (FOLFOX-4) versus FOLFOX-4 in the first-line treatment of metastatic colorectal cancer (mCRC): OPUS, a randomized phase II study. Abstract 4.
Commentary |
This trial is similar to the CRYSTAL trial, but evaluates FOLFOX4 in a much smaller study of 337 randomized patients. The best overall confirmed response rates were 45.6% in the chemotherapy plus cetuximab group and 35.7% in the group that received chemotherapy alone. Progression-free interval and overall survival were not reported. — Stuart M. Lichtman, M.D.
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