ISTANBUL, Turkey—A phase III trial has shown that XELOX is as effective as FOLFOX4 in patients with metastatic colorectal cancer, and that adding the targeted agent bevacizumab(Drug information on bevacizumab) (Avastin) to either regimen improves progressionfree survival (PFS). Roche announced the results of the NO16966 study earlier this year (see ONI September 2006, page 2), and more complete preliminary findings were presented at the 31st Congress of the European Society for Medical Oncology (LBA 3). “This is the largest trial so far in metastatic colorectal cancer and shows clearly that both regimens are equally effective,” said Jim Cassidy, MD, Beatson Oncology Centre, Glasgow.
The study initially was designed to compare XELOX—oxaliplatin (Eloxatin) 130 mg/m2 IV plus capecitabine(Drug information on capecitabine) (Xeloda) 1,000 mg/m2 orally twice daily on days 1 to 14, every 3 weeks—with FOLFOX4 consisting of leucovorin 200 mg/m2/d as a 2-hour infusion followed by bolus fluorouracil(Drug information on fluorouracil) (5-FU) 400 mg/m2/d and a 22- hour infusion of 5-FU 600 mg/m2/d repeated for 2 consecutive days every 2 weeks, plus oxaliplatin(Drug information on oxaliplatin) 85 mg/m2 on day 1 as a 2-hour infusion.
Patients on XELOX visit the clinic only once every 3 weeks for their oxaliplatin infusion, while those on FOLFOX4 must be hospitalized for 2 days every 2 weeks. A total of 634 patients were enrolled. In 2003, the protocol was amended to assess the benefits of bevacizumab 7.5 mg/kg IV vs placebo added to XELOX and FOLFOX4, and an additional 1,401 patients were recruited.
At a median follow-up of 18.6 months, PFS was similar: 8 months for XELOX vs 8.5 months for FOLFOX4. The incidence of adverse effects was also similar (71.5% vs 78.3%) but with a different pattern. Grade 3-4 diarrhea was more common with XELOX (20.2% vs 11.2%) and grade 3-4 myelosuppression was more common with FOLFOX4 (43.8% vs 7%).
Adding bevacizumab significantly improved PFS: Considering both arms together, patients receiving bevacizumab had a PFS of 9.4 months vs 8 months for placebo (P = .0023). Subgroup analysis showed that bevacizumab had a significant impact only in patients on XELOX (9.3 vs 7.4 months, P = .0026). For FOLFOX4 patients, PFS was 9.4 months with bevacizumab vs 8.6 months with placebo (P = .1871). Dr. Cassidy noted that many patients in the FOLFOX4/placebo arm had received previous adjuvant therapy and therefore may have had a better baseline prognosis.