Premalignant Colonic Adenomas, Gastric Polyps, Associated with Vemurafenib Treatment

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(ChemotherapyAdvisor)–The first observed premalignant colonic adenomas and gastric polyps associated with a BRAF inhibitor have been reported in three patients being treated for BRAF V600E melanoma with vemurafenib, investigators told those attending the Society for Melanoma Research 2012 Congress, held in Hollywood, CA.

“These findings may have significant implications for clinical management of patients treated with BRAF inhibitors,” stated Paul B. Chapman, MD, of Memorial Sloan-Kettering Cancer Center, New York, NY, USA, and colleagues.

Preclinical models suggest BRAF inhibitors can induce cutaneous squamous cell carcinoma “through paradoxical MAPK activation and RAS mutation,” they noted. However, “the risk of noncutaneous BRAF inhibitor-induced neoplasia is unknown.”

Four of 8 patients with BRAF V600E mutation melanoma treated for more than 2 years on a phase 1 trial of vemufarenib underwent esophagogastroduodenoscopy and colonoscopy.

Three patients—with a median age of 60 years—had multiple colonic adenomas and/or hyperplastic gastric polyps, they found. The first patient, who had a negative endoscopy 5 months before initiation of vemufarenib, presented with gastrointestinal bleeding “and was found to have four colonic adenomas, one hyperplastic colonic polyp, six gastric polyps (>2 cm), and a bleeding duodenal ulcer,” Dr. Chapman reported.

The second patient had six colonic adenomas, one hyperplastic colonic polyp, and no gastric polyps. The third patient had 10 colonic polyps and no gastric polyps. All three patients had their lesions resected and resumed treatment with vemurafenib 720-960mg bid. The fourth patient, age 37 years, had no polyps but unexplained ileal granulomas. None of the patients had a family history of colon cancer or polyposis.

After 6 months of retreatment, the first patient developed six recurrent gastric polyps and no colonic polyps; the second patient had no new findings.

“While multiple colonic adenomas can be found in this age group, the development of multiple colonic adenomas within 3 years of a negative colonoscopy, and the regrowth of multiple gastric polyps within 6 months of resection in [a] patient is highly unlikely to have occurred by chance,” they concluded.

Abstract (search using “Chapman” as the key word).

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