Association of sulindac and erlotinib vs placebo with colorectal neoplasia in familial adenomatous polyposis: Secondary analysis of a randomized clinical trial

IMPORTANCE Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for colorectal polyps and cancer. A combination of sulindac and erlotinib led to a 71% reduction in duodenal polyp burden in a phase 2 trial. OBJECTIVE To evaluate effect of sulindac and erlotinib on colorectal adenoma regression in patients with FAP. DESIGN, SETTING, AND PARTICIPANTS Prespecified secondary analysis for colorectal adenoma regression was carried out using data from a double-blind, randomized, placebo-controlled trial, enrolling 92 patients with FAP, conducted from July 2010 to June 2014 in Salt Lake City, Utah. INTERVENTIONS Patients were randomized to sulindac, 150 mg twice daily, and erlotinib, 75 mg daily (n = 46), vs placebo (n = 46) for 6 months. MAIN OUTCOMES AND MEASUREMENTS The total number of polyps in the intact colorectum, ileal pouch anal anastomosis, or ileo-rectum were recorded at baseline and 6 months. The primary outcomes were change in total colorectal polyp count and percentage change in colorectal polyps, following 6 months of treatment. RESULTS Eighty-two randomized patients (mean [SD] age, 40 [13] years; 49 [60%] women) had colorectal polyp count data available for this secondary analysis: 22 with intact colon, 44 with ileal pouch anal anastomosis and 16 with ileo-rectal anastomosis; 41 patients received sulindac/erlotinib and 41 placebo. The total colorectal polyp count was significantly different between the placebo and sulindac-erlotinib group at 6 months in patients with net percentage change of 69.4% in those with an intact colorectum compared with placebo (95% CI, 28.8%-109.2%; P = .009). CONCLUSION AND RELEVANCE In this double-blind, placebo-controlled, randomized trial we showed that combination treatment with sulindac and erlotinib compared with placebo resulted in significantly lower colorectal polyp burden after 6 months of treatment. There was a reduction in polyp burden in both those with an entire colorectum and those with only a rectal pouch or rectum.