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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