In the introduction to their paper, Dr. Volker Heinemann at Klinikum Muenchen-Grosshadern and colleagues explain that survival in metastatic colorectal cancer has been improved with the combinations of capecitabine and irinotecan (CAPIRI) and capecitabine with oxaliplatin (CAPOX). The authors’ current phase II study investigated the efficacy and safety of CAPIRI or CAPOX combined with cetuximab for the first-line treatment of metastatic colorectal cancer.
The investigators randomly assigned 185 patients to cetuximab (400 mg/m² day 1, followed by 250 mg/m² weekly) plus CAPIRI or to cetuximab plus CAPOX (
In the intention-to-treat analysis of 177 patients, the overall response rate was 46% for CAPIRI plus cetuximab versus 48% for CAPOX plus cetuximab, according to the report.
Dr. Heinemann and colleagues note that analysis of the KRAS gene mutational status to predict response to anti-EGFR treatment has become a standard of care, and KRAS status was ascertained in 81.4% of the intention-to-treat population.
However, they found that response rates were independent of KRAS status; 50.0% with wild-type KRAS versus 48.5% with mutant KRAS in the CAPIRI/cetuximab arm and 44.9% versus 50.0% in the CAPOX/cetuximab arm. Similarly, wild-type versus mutant KRAS status had little effect on progression-free survival in the two arms: 6.2 v 5.8 months, and 7.1 v 6.5 months, respectively.
With regard to grade 3/4 hematologic adverse events, rates of anemia were higher in patients treated with CAPIRI/cetuximab (3.4%) than CAPOX/cetuximab (0%), rates of leucopenia were 5.6% vs 3.4%, and neutropenia 9% vs 1.1%.
More than 80% of patients in both treatment groups had cetuximab-related acneiform exanthema/desquamation.
“In conclusion, this trial demonstrates that the regimens combining cetuximab with CAPIRI or CAPOX have similar activity,” Dr. Heinemann and colleagues write. “They are safe treatment options for first-line therapy of metastatic colorectal cancer.”
As for why KRAS gene mutation status did not correlate with overall response rate or progression-free survival, that “needs to be addressed by future investigations.”
Cetuximab Plus Capecitabine and Irinotecan Compared With Cetuximab Plus Capecitabine and Oxaliplatin As First-Line Treatment for Patients With Metastatic Colorectal Cancer: AIO KRK-0104—A Randomized Trial of the German AIO CRC Study Group
J Clin Oncol 2011;28.