Postmarketing Colitis Cases May Be Associated With Alpelisib Use

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In a research letter in JAMA Oncology, Sullivan et al described details of postmarketing cases of noninfectious colitis in patients with breast cancer reported to the U.S. Food and Drug Administration that were considered possibly or probably related to alpelisib treatment.

Key Findings

A total of 20 patients with colitis temporally associated with alpelisib use were identified from reports through February 28, 2021. Patients had a mean age of 54 years (range = 36–74 years).

Cases with a diagnostic confirmation of colitis (eg, histologic findings or radiologic imaging) or requiring immunosuppressive therapy to control diarrhea were considered category I (highest level of evidence); cases with limited diagnostic or treatment information were considered category II. Among the 20 cases, 15 were considered category I and 5 were category II.

Causality assessment indicated that 4 cases were probably, and 16 possibly, related to alpelisib use. Of 18 patients with case reports including information on time to onset, 13 (72%) had onset within 6 months of starting alpelisib.

Alpelisib was interrupted in 9 patients and discontinued in 11 due to colitis. Among 12 patients with case reports providing such information, 3 had positive rechallenge (recurrence of colitis after reintroduction of alpelisib at any dose) and 9 had positive dechallenge (permanent discontinuation of alpelisib or resumption of treatment at a reduced dose after resolution of colitis).

All patients had at least 1 serious outcome, including hospitalization in 19, intestinal perforation in 4, and death in 2.

The investigators stated, “In this case series, the findings support alpelisib as a likely cause of colitis on the basis of temporality and positive dechallenge/rechallenge. Affected individuals exhibited serious outcomes that may have been averted with early recognition and intervention…. Inhibition of the PI3K pathway plays a complex role in regulating proinflammatory and anti-inflammatory pathways. Drugs considered PI3K inhibitors, including alpelisib, may disrupt the anti-inflammatory pathways protecting the gastrointestinal tract….  Notably, the U.S. prescribing information of other orally administered PI3K inhibitors (duvelisib, idelalisib, umbralisib) contains a warning/precaution for colitis.”

Kathleen Sullivan, PharmD, BCOP, of the Division of Pharmacovigilance, Office of Surveillance and Epidemiology, Center for Drug Evaluation, U.S. FDA, is the corresponding author for the JAMA Oncology article.

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