| General information |
| Database: | DB00303 |
| Objective: | Since the 1990s, fluorouracilbased adjuvant chemotherapy has significantly reduced the risk of tumour recurrence in patients with stage III colon cancer. This study aimed to assess whether the addition of cetuximab to standard adjuvant oxaliplatin, fluorouracil, and leucovorin chemotherapy (FOLFOX4) in patients with stage III colon cancer improved diseasefree survival (DFS). |
| Authors: | Taieb J, et al |
| Title: | Oxaliplatin, fluorouracil, and leucovorin with or without cetuximab in patients with resected stage III colon cancer (PETACC8): an openlabel, randomisedphase 3 trial. |
| Journal: | Lancet Oncol. |
| Year: | 2014 |
| PMID: | 24928083 |
| Trial Design |
| Clinical Trial Id: | EudraCT 200500346323 |
| Agent: | cetuximab
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | colorectal cancer |
| Cancer Subtype: | resected stage III colon cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | standard adjuvant oxaliplatin, fluorouracil, + leucovorin chemotherapy (FOLFOX4)¡Àcetuximab |
| Study Type: | an openlabel, randomisedphase III trial |
| Key Patients Feature: | patients aged between 18 and 75 years with pathologically confirmed stage III colon adenocarcinoma. Other main inclusion criteria were: a KRAS exon 2 wildtype tumour (following the June 17, 2008, protocol amendment), curative (R0) resection at least 28 days before the start of treatment and between 14 and 56 days before randomisation, WHO performance status 0 or 1, life expectancy of 5 years or longer, adequate haematological and organ function, carcinoembryogenic antigen less than 1.5 times the upper limit of normal after surgery, and signed written informed consent. |
| Biomarker: | KRAS gene (KRAS exon 2 wildtype). |
| Biomark Analysis: | in patients with KRAS exon 2/BRAF wildtype (n=984, HR 0.99; 95% CI 0.761.28) or KRAS exon 2mutated tumours (n=742, HR 1.06; 95% CI 0.821.37). |
| Control Group Info: | FOLFOX4 alone |
| Treatment Info: | they randomly assigned patients with resected (R0) stage III disease (1:1) to receive 12 cycles of FOLFOX4 twice a week with or without cetuximab. patients were stratified by Nstatus (N1 vs N2), Tstatus (T13 vs T4), and obstruction or perforation status (no obstruction and no perforation vs obstruction or perforation or both). A protocol amendment (applied in June, 2008, after 2096 patients had been randomly assigned to treatmentrestricted enrolment to patients with tumours wildtype at codons 12 and 13 in exon 2 of the KRAS gene (KRAS exon 2 wildtype). |
| Primary End Point: | DFS |
| Secondary End Point: | overall survival (including 5year and 7year survival), treatment compliance, the identification of prognostic and predictive factors for relapse or treatment efficacy or both, and the safety profile. |
| Patients Number: | 2559 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | They noted heterogeneous responses to the addition of cetuximab in preplanned subgroup analyses. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | In the experimental and control groups, DFS was similar in the intentiontotreat population (hazard ratio [HR] 1.05; 95% CI 0.851.29; p=0.66), and in patients with KRAS exon 2/BRAF wildtype (n=984, HR 0.99; 95% CI 0.761.28) or KRAS exon 2mutated tumours (n=742, HR 1.06; 95% CI 0.821.37). |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Grade 3 or 4 acnelike rash (in 209 of 785 patients [27%] vs four of 805 [<1%]), diarrhoea (113 [14%] vs 70 [9%]), mucositis (63 [8%] vs 10 [1%]), and infusionrelated reactions (55 [7%] vs 30 [4%]) were more frequent in patients treated with FOLFOX4 plus cetuximab than in those patients who received FOLFOX4 alone. |
| Conclusions: | The addition of cetuximab to FOLFOX4 did not improve DFS compared with FOLFOX4 alone in patients with KRAS exon 2 wildtype resected stage III colon cancer. This trial cannot conclude on the benefit of cetuximab in the studied population, but the heterogeneity of response suggests that further investigation of the role of FOLFOX4 plus cetuximab in specific patient subgroups is warranted. |