Erlotinib lowers polyp burden in familial adenomatous polyposis

Treatment with erlotinib is well tolerated and leads to a reduction in duodenal and lower gastrointestinal (GI) polyp burden in patients with familial adenomatous polyposis (FAP), according to data from a phase II trial.

The single-arm trial included 46 FAP patients (mean age 44.1 years, 48 percent women) who took 350 mg of erlotinib orally once a week for 6 months. The primary endpoints were duodenal polyp burden (sum of polyp diameters; assessed in the proximal duodenum by esophagogastroduodenoscopy) and rate of grade 2–3 adverse events (AEs) at 6 months.

Researchers also evaluated total duodenal polyp count, along with changes in lower GI polyp burden and count (for participants examined by optional lower endoscopy), as the secondary endpoint.

Forty-two patients completed 6 months of treatment and were included in the per-protocol analysis. Duodenal polyp burden decreased significantly after 6 months of treatment, with a mean change of −29.6 percent (95 percent confidence interval [CI], −39.6 to −19.7) from baseline (p<0.0001).

Similar results were obtained in the subgroup of patients with advanced duodenal polyposis (Spigelman 3), with duodenal polyp burden reduced by 27 percent (95 percent CI, −38.7 to −15.2) at 6 months (p<0.0001). Of note, Spigelman stage moved from a more to a less threatening stage in 12 percent of patients.

Lower GI polyp number also dropped after 6 months of erlotinib treatment (median, −30.8 percent; p=0.0256).

Nearly a quarter of the population (71.7 percent) had grade 2–3 AEs. However, these AEs were mostly lower grade, and only two patients experienced grade 3 toxicity at least possibly related to treatment.

The findings highlight the potential of erlotinib as an acceptable chemopreventive agent for FAP-associated GI polyposis and warrant further investigation of the drug.