Polyp Burden Drops With Sulindac/Erlotinib Combo in FAP

Patients with familial adenomatous polyposis (FAP) have an increased risk for colorectal polyps and cancer; however, treatment with a combination of sulindac and erlotinib reduced their colorectal polyp burden by more than two thirds after 6 months compared with placebo, according to a secondary analysis of data from the FAPEST trial published in JAMA Oncology.

Treatment with sulindac and erlotinib also resulted in a higher rate of adverse events, including acneiform cutaneous eruption (68%) and oral mucositis (32%).

“This preliminary trial lays the groundwork for future chemoprevention efforts,” wrote researcher N. Jewel Samadder, MD, MSc, of Mayo Clinic, and colleagues. However, they added that the study also leaves “many important questions unanswered,” including “whether prolonged treatment with these medications can replace, delay the need for, or limit the anatomical extent of proctocolectomy and whether such treatment can inhibit progression to cancer.”

Results of the phase II randomized, placebo-controlled FAPEST trial showed that combination treatment with erlotinib and sulindac resulted in a 71% reduction in duodenal polyp burden after 6 months on treatment. The trial randomly assigned 82 patients with FAP to therapy with sulindac at a dosage of 150-mg twice daily plus erlotinib at 75-mg daily or placebo for 6 months. Patients were evaluated at baseline and 6 months for the total number of polyps in the intact colorectum, ileal pouch anal anastomosis, or ileorectum.

In this secondary analysis, the researchers looked at data from FAPEST to assess the effect of the drug combination on colorectal adenoma formation and regression in patients with FAP. Of the 82 patients randomized, 22 had an intact colon, 44 had ileal pouch anastomosis, and 16 had ileorectal anastomosis.

Total polyp count was significantly lower in patients treated with the study drugs at 6 months compared with placebo (change in polyp number, −5.1; 95% CI, −6.4 to −3.5; P < .001). This was a percentage change in colorectal polyp number, showing a net decrease of 69.4% in colorectal polyp number from baseline in the treatment group compared with placebo (95% CI, 28.8% to 109.2%; P = .04).

Among patients with ileal pouch anal anastomosis, there was a median decrease of four polyps from baseline in the sulindac/erlotinib group and a 1-polyp increase in the placebo group (group difference:14.5; 95% CI, 3.5 to 28.1; P = .003).

The majority of patients assigned to sulindac/erlotinib experienced some type of adverse event, including 33% of patients who had grade 2 or 3 adverse events. Significantly more patients assigned to receive the study drugs had acneiform-like cutaneous eruption compared with placebo (68.3% vs 22%; P < .001). Erlotinib dose reductions occurred in 28% of the placebo group compared with 73% of patients in the treatment group.

“Whereas the dosing of sulindac was based on prior chemoprevention studies, the dosing of erlotinib was estimated from cancer treatment and lung cancer chemotherapy trials,” the researchers noted. “Dose ranging studies will be needed to determine if lower and/or less frequent dosing of erlotinib could diminish these adverse effects but retain efficacy.”