Sanoff HK, et al. - In this international, double-blind, placebo-controlled, multicenter trial, researchers evaluated the effectiveness of regorafenib with folinic acid, fluorouracil, and irinotecan (FOLFIRI) as second-line treatment for metastatic colorectal cancer. They found that only modestly prolonged progression-free survival (PFS) was achieved with the addition of regorafenib to FOLFIRI as second-line therapy for metastatic colorectal cancer vs FOLFIRI alone.

Methods

• Enrollment of patients with metastatic colorectal cancer who progressed on first-line oxaliplatin and fluoropyrimidine was carried out at 45 sites in the US and Ireland.
• Patients were stratified by prior bevacizumab use and were randomly allocated 2:1 to regorafenib or placebo.
• Patients were administered FOLFIRI on days 1 and 2 and days 15 and 16 with 160 mg of regorafenib or placebo on days 4 to 10 and days 18 to 24 of every 28-day cycle.
• Crossover was not allowed.
• Progression-free survival (PFS) was primary endpoint.
• A total of 180 patients were needed for 135 events to achieve 90% power to detect a hazard ratio (HR) of 0.65 with a 1-sided α value of .1, under the assumption of a 75% event rate.

Results

• A total of 181 patients with a median age of 62 years were randomized (120 to regorafenib-FOLFIRI and 61 to placebo-FOLFIRI); previously bevacizumab or aflibercept was used by 117 (65%) of these.
• A longer PFS was seen with regorafenib-FOLFIRI vs placebo-FOLFIRI (median, 6.1 vs 5.3 months; HR, 0.73; 95% confidence interval [CI], 0.53-1.01; log-rank P=.056), but longer median overall survival was not seen (HR, 1.01; 95% CI, 0.71-1.44).
• A higher response rate was observed with regorafenib-FOLFIRI (34%; 95% CI, 25%-44%) vs placebo-FOLFIRI (21%; 95% CI, 11%-33%; P=.07).
• Diarrhea, neutropenia, febrile neutropenia, hypophosphatemia, and hypertension were documented as grade 3/4 adverse events with a > 5% absolute increase from regorafenib.