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4030 Background: The combination of Bev with 5-FU/FA and irinotecan or oxaliplatin is highly active in ACRC. A recent phase III trial demonstrated that infusional 5-FU and capecitabine (cape) have comparable efficacy when combined with oxaliplatin and Bev (Cassidy et al. 2007). In contrast, data are heterogeneous for cape/irinotecan combinations. This randomized phase II trial compared safety and efficacy of Bev with either CapOx or CapIri as first line therapy in ACRC. Methods: Prerequisites were: untreated ACRC, ECOG PS≤2, measurable lesion(s), adequate hematologic and organ functions. Primary endpoint in this non- comparative design was progression-free survival (PFS) rate after 6 months (mos). Regimen: Bev 7.5 mg/kg day (d)1 with either oxaliplatin (130 mg/m2 d1)/cape (1,000 mg/m2 bid d1–14; CapOx/Bev, arm A) or irinotecan (200 mg/m2 d1)/cape (800 mg/m2 bid d 1–14; CapIri/Bev, arm B), all q d22. Arm B doses were reduced by 20% for both, cape and irinotecan, compared to previous trials reporting unacceptable GI toxicity (Köhne et al., Ann Oncol 2007; Fuchs et al., J Clin Oncol 2007). Results: From July 2005 to Oct 2006, 255 patients (pts) were randomised. Patient characteristics (arm A/B): Median age 64/65 yrs, male 67%/68%, ECOG 0/1/2 52/45/3% and 52/45/2%, colon 60%/64%, rectum 40%/36%, respectively. Data are available for 244 (124/120) pts. Treatment characteristics (arm A/B): A total of 965/1069 cycles (median 8/9 cycles) have been administered. For 198 pts the end of treatment has been documented: 34% (30%/38%) due to progression, 29% (41%/18%) due to toxicity, 20% (16%/24%) because of pts´ decision. Most common CTC gr. 3/4 toxicities of pts, arm A/B: Diarrhea 19%/15%, hand-foot-syndrome 10%/7%, peripheral neuropathy 23%/0% Tumor response rates (CR+PR) were 54%/55%, tumor control rates (incl. SD) were 79%/80%. PFS rate at 6 mos were 78%/84%, median PFS 9.9/12.5 mos. Conclusions: Both regimen are highly active and safe. The absense of neuropathy favours the CapIri/Bev combination. Interestingly, the dose reduction of CapIri seemingly improves tolerability without compromising efficacy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche Pharma, sanofi-aventis Merck, Roche Pharma, sanofi-aventis GmbH Merck, Roche Pharma, sanofi-aventis GmbH Roche Pharma GmbH, sanofi-aventis GmbH
Reinacher-Schick et al. (Tue,) studied this question.