Alectinib and gastrointestinal perforation in ALK-rearranged non-small cell lung cancer: A case series.

Abstract

Background: Alectinib, a second-generation ALK inhibitor, is used in first-line and adjuvant treatment for ALK-rearranged NSCLC, and has proven to be both effective and well tolerated. Gastrointestinal (GI) perforation is an extremely rare but potentially life-threatening complication, with only sporadic cases reported in the literature.

Methods: We describe, to the best of our knowledge, the largest case series to date of GI perforations that occurred during alectinib treatment in patients with ALK-rearranged NSCLC. Clinical features, management strategies, and outcomes were analyzed and integrated with available literature.

Results: Three female patients developed GI perforation after variable durations of alectinib treatment, ranging from one month to over three years. Two cases were associated with pre-existing diverticulosis, while one occurred in the absence of any known GI comorbidities. Management included conservative treatment with intravenous antibiotics in two cases and surgical intervention in one. Alectinib was permanently discontinued in all patients. Subsequent therapeutic strategies included lorlatinib or brigatinib, with heterogeneous tolerability and outcomes. Literature review identified other reports of GI perforation or severe toxicity under alectinib.

Conclusions: Although rare, GI perforation, represents a clinically relevant adverse event associated with alectinib, particularly in patients with diverticulosis or other predisposing conditions. It is essential to optimize safety and long-term disease control by raising awareness of early warning symptoms, conducting a baseline GI evaluation in high-risk patients and carefully sequencing therapy after discontinuation.