Efficacy and safety of bevacizumab (BEV) plus chemotherapy in Chinese patients (pts) with metastatic colorectal cancer (mCRC): Results from the ARTIST study.

Abstract

e14002 Background: BEV inhibits tumor angiogenesis by targeting vascular endothelial growth factor (VEGF). This randomized open-label multicenter study (ARTIST) evaluated the efficacy and safety of BEV in combination with modified IFL (mIFL) as first-line treatment for Chinese pts with mCRC. Methods: Pts >18 years with histologically confirmed, previously untreated, measurable mCRC and ECOG PS 0 or 1 were randomized 2:1 to BEV + mIFL or mIFL alone until disease progression, death, or unacceptable toxicities. mIFL (irinotecan 125 mg/m2, leucovorin 20 mg/m2 bolus, and 5-FU 500 mg/m2) was given weekly for 4 weeks every 6 weeks. BEV 5 mg/kg was given on Day 1 with chemotherapy, then every 2 weeks. Primary objectives were progression-free survival (PFS) and 6-month PFS rate; secondary objectives included overall survival (OS), overall response rate (ORR), response duration, and safety. Results: Between Jul 07 and Aug 08, 214 pts were enrolled at 12 centers in China (203 pts evaluable); final analysis was performed 10 months after the last pt was enrolled. Pt characteristics were balanced between arms. Addition of BEV to chemotherapy significantly improved PFS, 6-month PFS, OS, and ORR (table); risk of disease progression or death was reduced by 56% and risk of death by 38%. BEV plus mIFL was well tolerated; no grade 4/5 adverse events (AEs) of special interest, wound-healing complications, or episodes of congestive heart failure were reported (for grade 3 AEs see Table). Conclusions: The ARTIST study has shown that BEV plus mIFL is effective and well tolerated as first-line therapy for mCRC. The clinical benefit and safety profiles of BEV in Chinese pts are consistent with those observed in pivotal phase III multinational studies. Outcome (95% CI) BEV + mIFL mIFL p value Efficacy Evaluable patients 139 64 6-month PFS, % 62.6 (54.5–70.6) 25.0 (14.4–35.6) p<0.001 Median PFS, months 8.3 (7.4–8.9) 4.2 (3.7–4.9) p<0.001 HR=0.44 (0.31–0.63) Median OS, months 18.7 (15.8–19.6) 13.4 (9.7–17.2) p=0.014 HR=0.62 (0.41–0.95) ORR, % 35.3 (27.5–43.5) 17.2 (8.4–27.7) p=0.013 Safety Evaluable patients 141 70 Grade 3 hypertension, % 3.5 0 Grade 3 bleeding, % 0.7 1.4 Grade 3 GI perforation, % 0.7 0 No significant financial relationships to disclose.