Alpelisib是一种口服的特异性PI3K抑制剂，与fulvestrant联合使用，用于治疗HR+/HER2-/PIK3CA突变转移性乳腺癌患者。与alpelisib的药物不良反应很常见，包括高血糖和皮疹。在这里，我们描述了两例进行alpelisib治疗的逐渐恶化的PIK3CA突变转移癌患者出现了超出皮疹的非常规和危及生命的反应。Case-A（阴道癌）：在治疗10天后，她出现了干眼症、全身皮疹和瘙痒。中断了alpelisib，并进行了症状性治疗。由于肿瘤有初步的反应，重新尝试了治疗。减少alpelisib的剂量后90分钟，她出现了过敏反应，伴有血管性水肿、低血压和皮疹。Case-B（乳腺癌）：在治疗11天后，她出现了皮疹，中断了alpelisib。重新开始使用时，她感到脸部和耳朵有刺痛感和一些皮肤红斑。鉴于轻微的皮疹，进行了带有预防措施的第二次再次尝试。减少alpelisib的剂量90分钟后，她出现了I型过敏反应，伴有血管性水肿、刺痛和皮疹。在这两种情况下，确诊为I型过敏反应，进行了症状性治疗，永久停止使用alpelisib，患者在接下来的一周（多周）完全康复。本报告强调在与alpelisib相关的皮疹的鉴别诊断中，考虑I型过敏反应的重要性。即使在治疗几天后出现反应，也不能排除I型过敏反应的可能性。再次尝试可能是危险的，应始终仔细考虑或甚至避免。© The Author(s) 2023. Published by Oxford University Press.

Alpelisib is a specific oral PI3K inhibitor used combined with fulvestrant for the treatment of patients with HR+/HER2-/PIK3CA-mutated metastatic breast cancer. Adverse drug reactions with alpelisib are common, including hyperglycemia and rash. Here we describe extraordinary and life-threatening reactions beyond skin rash in two patients with progressive PIK3CA-mutated metastatic cancer in whom alpelisib was initiated. Case-A (vaginal cancer): After 10 days on treatment, she developed dry eyes, generalized rash and itching. Alpelisib was interrupted and symptomatic treatment initiated. Because of an initial tumor response, a rechallenge was done. Ninety minutes after a reduced dose of alpelisib, she developed an anaphylactic reaction with angioedema, hypotension, and skin rash. Case-B (breast cancer): After 11 days on treatment, she developed skin rash and alpelisib was interrupted. At re-initiation, she felt tingles in her face and ears and some skin erythema. Given the mild rash, a second rechallenge with premedication was performed. Ninety minutes after a reduced dose of alpelisib, she developed a type-1 allergic reaction with angioedema, tingles, and skin rash. In both cases, a type-1 allergic reaction was diagnosed and symptomatic treatment was initiated, alpelisib was permanently discontinued and the patients fully recovered the next week(s). This report underlines the critical importance to consider type-I allergic reactions in the differential diagnosis in cases of rash associated with alpelisib. Even if a reaction develops after days on treatment, a type-I allergic reaction cannot be excluded. A rechallenge can be dangerous and should always be well contemplated or even avoided.© The Author(s) 2023. Published by Oxford University Press.