Alpelisib-induced severe interstitial lung disease: case report

Alpelisib, a selective phosphatidylinositol-3-kinase alpha (PI3Kα) inhibitor, improves outcomes in hormone receptor-positive (HR+), HER2-negative, PIK3CA-mutated advanced breast cancer, but rare serious toxicities such as pneumonitis may occur. We report a 79-year-old non-smoking woman with ER-positive/HER2-negative breast cancer who initially underwent breast-conserving surgery and adjuvant anastrozole in December 2023. Following local recurrence in October 2024, she received mastectomy and ribociclib-fulvestrant. Disease progression with nodal and osseous metastases was detected in April 2025. Liquid biopsy revealed a PIK3CA H1047R mutation, and alpelisib 150 mg daily plus fulvestrant was initiated in May 2025. After two months, she developed acute dyspnea and hypoxemia without fever. Imaging showed bilateral peripheral ground-glass opacities outside prior radiation fields, and infectious work-up was negative. Bronchoalveolar lavage supported drug-induced pneumonitis. Alpelisib was discontinued, and high-dose corticosteroids led to complete clinical and radiological resolution. This case highlights early-onset alpelisib-induced pneumonitis at a reduced dose and underscores the importance of early recognition and prompt management.