CHARTA: FOLFOX+bevacizumab +/- irinotecan in advanced colorectal cancer (CRC)—Final results of the randomized phase II trial of the AIO (KRK 0209).

Abstract

658 Background: The 4-drug-regimen FOLFOXIRI+Bevacizumab (Bev) was superior to FOLFIRI+Bev (TRIBE F.Loupakis, NEJM 2014). CHARTA investigates the same 4-drug-regimen vs. FOLFOX+Bev. Methods: 250 patients were randomized from 7/11 to 12/14 to standard FOLFOX+Bev (A) vs. FOLFOXIRI+Bev (B), with dose/schedule as in TRIBE, 25% dose reduction in cycle 1 + 2, if necessary. Incl.criteria: ECOG 0-2, ≥ 1 measurable lesion > 1cm; stratified by ESMO-Group 1, 2, 3 (HJ Schmoll et. al., Ann Oncol 2012). Induction: 6 months, maintenance Capecitabine+Bev until progression or max. of 12 months, with reinduction by individual decision. Primary EP: significant improvement of PFS-rate at 9 months (p<0.1, 2-sided Fisher’s-exact test); secondary EP: RR- rate, PFS, OS, sec. resection. Results: Evaluable 241 pts. (1 not elig., 8 prot. violation); m/f: 65%/35%, age 61 yrs. (21-82), left/right: left A: 51, 5%, B: 48, 5%; right A: 45%, B: 55%; ECOG 0-1/2: 96% / 4%, ESMO-group 1/2/3: 29%/ 55%/ 16%. Primary endpoint was met: significantly improved PFS at 9 months 56% vs. 68% (p= 0,086). Preliminary PFS 9,76 vs. 12,0 months (HR 0.77, p=0.61), identical to TRIBE: 9.7 vs. 12.1. Response (A/B): CR: 5/5%, CR/PR 60/70%, SD 25/21%, PD 14/9%; sec. resection: 21/23%. Subgroup - analyses did not show significant differences, except CR / PR left/right (A/B): left 59/68%, right 63/73%; PFS (months) left 10.4/12 (HR 0.69, p=0.03), right: 8.2 /10.7); non-significant improvement in ESMO-group 3 (HR 0.51), RAS-wt (HR 0.67), Koehne-Score High risk HR 0.58; ECOG 1: HR 0.69. QL-Global- Health-Score: slightly worse in A, vs. improved in B. Dose-intensity <70%/ 70-90%/ >90% (A/B): 39/37%/ 18/26%/ 41%/36%; initial dose-reduction 17% of pts. Toxicity: low to moderate without major differences between A &B, except grade ¾ diarrhea 12/16%, neutrophils 14/20%, GI 12/20%. Conclusions: The 4-drug-regimen has superior activity with the same outcome as TRIBE and is well tolerated, without a negative effect of initial dose-reduction, and an improvement of global QoL-Score. Final PFS, OS data and detailed subgroup/multivariate analysis, including Quality of life data, will be presented. Clinical trial information: NCT01321957.