| General information |
| Database: | DB00952 |
| Objective: | Two arms with FOLFIRI, with or without cetuximab, were initially included in the randomizedphase III intergroup clinical trial NCCTG (North Central Cancer Treatment Group) N0147. When other contemporary trials demonstrated no benefit to using irinotecan as adjuvant therapy, the FOLFIRIcontaining arms were discontinued. they report the clinical outcomes for patients randomized to FOLFIRI with or without cetuximab |
| Authors: | Huang J, et al |
| Title: | Comparison of FOLFIRI with or without cetuximab in patients with resected stage III colon cancer; NCCTG (Alliance) intergroup trial N0147. |
| Journal: | Clin Colorectal Cancer |
| Year: | 2014 |
| PMID: | 24512953 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | stage III colon cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | FOLFIRI with cetuximab |
| Study Type: | phase III trial N0I47 |
| Key Patients Feature: | Eligible patients were age 18 years or older with Eastern Cooperative Oncology Group performance status of 0, 1, or 2, and histologically proven stage III (any T, N1 or N2, M0) adenocarcinoma of the colon, at least 12 cm from the anal verge. |
| Biomarker: | KRAS mutation |
| Biomark Analysis: | The addition of cetuximab showed a trend toward improved DFS (hazard ratio [HR], 0.53; 95% CI, 0.261.1; P = .09) and OS (HR, 0.45; 95% CI, 0.171.16; P = .10) in the overall group, regardless of KRAS status, and in patients with wild type KRAS. |
| Control Group Info: | single arm |
| Treatment Info: | After resection, patients were randomized to 12 biweekly cycles of FOLFIRI, with or without cetuximab. KRAS (Kirsten rat sarcoma viral oncogene homolog) mutation status was retrospectively determined in a central lab |
| Primary End Point: | diseasefree survival (DFS). |
| Secondary End Point: | overall survival (OS) and toxicity. |
| Patients Number: | 106 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | Cetuximab improved TTR with a hazard ratio (HR) of 0.54 (95% confidence interval [CI], 0.3-1.2; P = .12) and 3year TTR estimates of 87% (95% CI, 77%-98%) versus 69% (95% CI, 60%-78%) for FOLFIRI alone. |
| Median PFS A vs. C: | Improved DFS in cetuximab, (DFS HR, 0.53; 95% CI, 0.3-1.1; P = .09) and 3year eventfree estimates of 85% (95% CI, 74%-97%) versus 67% (95% CI, 59%-77%) for FOLFIRI alone |
| Median OS A vs. C: | Treatment with cetuximab showed a trend toward improved OS (OS HR, 0.45; 95% CI, 0.2-1.2; P = .10) with 3year survival estimates of 90% (95% CI, 81%-100%) versus 85% (95% CI, 78%-92%) for FOLFIRI alone |
| Adverse Event(agent arm): | Grade 3 or higher adverse events were reported more frequently among patients treated with cetuximab (53% vs. 68%; P = .11). Cetuximabtreated patients reported significantly more nonhematologic events (46% vs. 68%; P = .02). Grade more than and equal to 3 paresthesia, rash/acne, and infarctions were more common with FOLFIRI and cetuximab. One death occurred during treatment in the FOLFIRI arm. A 72yearold Caucasian man died suddenly 10 days after starting his 8th cycle due to a suspected pulmonary embolism. |
| Conclusions: | In this small randomized subset of patients with resected stage III colon cancer, the addition of cetuximab to FOLFIRI was associated with a nonsignificant trend toward improved DFS and OS. Nevertheless, considering the limitations of this analysis, FOLFOX without the addition of a biologic agent remains the standard of care for adjuvant therapy in resected stage III colon cancer. |