A subanalysis of the phase III N0147 clinical trial suggests that adding cetuximab (Erbitux) to the chemotherapy regimen FOLFIRI (leucovorin, fluorouracil [5-FU], irinotecan) may result in statistically significant improvements in outcomes for patients with stage III resected colon cancer, compared to treatment with FOLFIRI alone. Although researchers acknowledged that the number of patients in the FOLFIRI arms of the trial was small (n = 146), they noted that adding adjuvant cetuximab to FOLFIRI significantly improved disease-free and overall survival at 3 years.

In the analysis from researchers at the Mayo Clinic in Rochester, Minnesota, outcomes from 106 patients on FOLFIRI were compared to those of 40 patients on FOLFIRI/cetuximab at 3 years. Results of the analysis were reported at this year's Gastrointestinal Cancers Symposium.

Promising Trends

In the N0147 clinical trial, researchers found that disease-free survival was 86.6% with FOLFIRI plus cetuximab vs 66.7% for FOLFIRI alone, and overall survival was 91.8% for FOLFIRI-cetuximab vs 84.4% for FOLFIRI alone.

"Adjuvant FOLFIRI alone resulted in a 3-year disease-free survival that was lower than that expected for FOLFOX [leucovorin, 5-FU, oxaliplatin]," said presenting researcher Jocelin Huang, MD, of the Mayo Clinic in Rochester. "Although there were trends toward improved disease-free survival and overall survival with the addition of cetuximab to adjuvant FOLFIRI, the study may be too underpowered to make any firm conclusions," she added.

Yet the trial showed promising trends both for patients with KRAS mutant stage III colon cancer and for those with KRAS wild-type disease treated with FOLFIRI plus cetuximab. In patients with KRAS wild-type colon cancer (n = 95), disease-free survival was 92.3% with the addition of cetuximab vs 69.8% for FOLFIRI alone (P = .04, HR = 0.31).

Overall survival was also improved in these patients, from 85.2% with FOLFIRI alone to 92% with the addition of cetuximab, although the difference was not statistically significant, Dr. Huang said.

Among patients with KRAS mutant disease (n = 46), a trend toward improved disease-free and overall survival was again seen with the addition of cetuximab, although the difference between the two arms was not statistically significant. In patients with KRAS mutant disease, 3-year disease-free survival improved from 56.3% to 82.5%% with the addition of cetuximab, and overall survival was also significantly better with FOLFIRI/cetuximab-90.9% vs 80.6% for patients who received FOLFIRI alone.

Adverse Events and Discontinuation Rates

Despite the improved progression-free and overall survival seen by combining cetuximab with FOLFIRI, patients who received cetuximab were more likely to experience nonhematologic grade III adverse events (46% with FOLFIRI alone vs 68% with FOLFIRI/cetuximab, P = .02).

"Fewer patients in the cetuximab-containing arm were able to complete the study per protocol (70% with FOLFIRI/cetuximab vs 79% for FOLFIRI alone)," Dr. Huang said. The rate of discontinuation due to refusal or adverse events in the cetuximab arm was also double that in the FOLFIRI-alone arm, she added. ■

Reference

1. Huang J, Sargent DJ, Mahoney MR, et al: Adjuvant FOLFIRI with or without cetuximab in patients with resected stage III colon cancer: NCCTG Intergroup phase III trial N0147. Gastrointestinal Cancers Symposium. Abstract 363. Presented January 22, 2011.