Background: FOLFOX is standard adjuvant therapy for stage III colon cancer (CC). Adding cetuximab to FOLFOX benefits patients with metastatic KRAS wild-type (wt) CC. The addition of cetuximab to mFOLFOX6 in the adjuvant setting in the US N0147 trial, failed to show a benefit (1). PETACC8 assessed the potential benefit of cetuximab added to FOLFOX4. Methods: Patients with informed consent and centrally determined KRAS wt CC were randomized 28-56 days following resection. They received 12 biweekly cycles of oxaliplatin 85 mg/m2 on d1, with leucovorin 200 mg/m2, 5FU 400 mg/m2 bolus IV, then 22-hr IV 5FU 600 mg/m2 on d1 and d2 (FOLFOX4), without (Arm A) or with (Arm B) weekly cetuximab 250 mg/m2 (loading dose 400 mg/m2, cycle 1). Primary endpoint was disease-free survival time (DFS). Secondary endpoints included overall survival, treatment compliance and safety. Planned accrual of 1,407 KRAS wt patients provided a 90% power to detect a hazard ratio (HR) of 0.75 with 2-sided α = 0.05; an interim analysis was planned after 65% of the events. Results: 1,602 KRAS wt patients were included in the interim analysis (Arm A, 811; Arm B, 791) with a median follow-up of 39.6 months at the time of the interim analysis. No difference was seen between the arms for DFS (HR 1.05, 95% CI 0.85- 1.29; p = 0.66); the conditional power to have a positive result at the end of the study under a HR of 1.75 was lower than 1%. 3-yr DFS was 78.0% (95% CI 74.8-80.8) in Arm A and 75.1% (95% CI 71.7-78.1) in Arm B. The frequency of any AE grade ≥ 3 was significantly increased in Arm B (66.2% Arm A vs 80.9% Arm B; RR: 1.22, 95% CI 1.15-1.30). Diarrhea, vomiting, mucositis, skin disorders (grade ≥ 3) and failure to complete 12 cycles were also significantly higher in Arm B. Conclusions: The primary analysis of this randomized phase III trial has not shown a benefit for adding cetuximab to FOLFOX4 in patients with resected stage III KRAS wt CC. Subgroup and biomarker analyses are still ongoing. Supported by Merck-Serono, Sanofi-Aventis.
Adjuvant FOLFOX4 +/- cetuximab in kras wildtype patients with resected stage III colon cancer results from the PETACC8 Intergroup Trial / Taieb J, Tabernero J, Mini E, Subtil F, Folprecht G, Van Laethem JL, Thaler J, Bridgewater J, Sanches E, Nørgård Petersen L, Rougier P, Collette L, Praet M, Girault C, Schneider M, Squifflet P, Laurent-Puig P, Van Cutsem E, Bedenne L, Lepage C.. - In: ANNALS OF ONCOLOGY. - ISSN 0923-7534. - STAMPA. - 23 Suppl 4:(2012), pp. 17-17.
Adjuvant FOLFOX4 +/- cetuximab in kras wildtype patients with resected stage III colon cancer results from the PETACC8 Intergroup Trial
MINI, ENRICO;
2012
Abstract
Background: FOLFOX is standard adjuvant therapy for stage III colon cancer (CC). Adding cetuximab to FOLFOX benefits patients with metastatic KRAS wild-type (wt) CC. The addition of cetuximab to mFOLFOX6 in the adjuvant setting in the US N0147 trial, failed to show a benefit (1). PETACC8 assessed the potential benefit of cetuximab added to FOLFOX4. Methods: Patients with informed consent and centrally determined KRAS wt CC were randomized 28-56 days following resection. They received 12 biweekly cycles of oxaliplatin 85 mg/m2 on d1, with leucovorin 200 mg/m2, 5FU 400 mg/m2 bolus IV, then 22-hr IV 5FU 600 mg/m2 on d1 and d2 (FOLFOX4), without (Arm A) or with (Arm B) weekly cetuximab 250 mg/m2 (loading dose 400 mg/m2, cycle 1). Primary endpoint was disease-free survival time (DFS). Secondary endpoints included overall survival, treatment compliance and safety. Planned accrual of 1,407 KRAS wt patients provided a 90% power to detect a hazard ratio (HR) of 0.75 with 2-sided α = 0.05; an interim analysis was planned after 65% of the events. Results: 1,602 KRAS wt patients were included in the interim analysis (Arm A, 811; Arm B, 791) with a median follow-up of 39.6 months at the time of the interim analysis. No difference was seen between the arms for DFS (HR 1.05, 95% CI 0.85- 1.29; p = 0.66); the conditional power to have a positive result at the end of the study under a HR of 1.75 was lower than 1%. 3-yr DFS was 78.0% (95% CI 74.8-80.8) in Arm A and 75.1% (95% CI 71.7-78.1) in Arm B. The frequency of any AE grade ≥ 3 was significantly increased in Arm B (66.2% Arm A vs 80.9% Arm B; RR: 1.22, 95% CI 1.15-1.30). Diarrhea, vomiting, mucositis, skin disorders (grade ≥ 3) and failure to complete 12 cycles were also significantly higher in Arm B. Conclusions: The primary analysis of this randomized phase III trial has not shown a benefit for adding cetuximab to FOLFOX4 in patients with resected stage III KRAS wt CC. Subgroup and biomarker analyses are still ongoing. Supported by Merck-Serono, Sanofi-Aventis.
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