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. 2023 Jul 5;28(7):e493-e497.
doi: 10.1093/oncolo/oyad092.

Beyond Skin Rash: Alpelisib-Induced Anaphylactic Reactions

Tim Schutte  1 , Laurien J Zeverijn  2 , Birgit S Geurts  2 , Gijsbrecht F de Wit  2 , Marleen Kok  3 , Frans L Opdam  3
Affiliations

Beyond Skin Rash: Alpelisib-Induced Anaphylactic Reactions

Tim Schutte et al. Oncologist. .

Abstract

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.

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Conflict of interest statement

Laurien Zeverijn, Birgit Geurts, and Gijs de Wit have received grants and non-financial support from Novartis in the context of the Drug Rediscovery Protocol, not related to the research, authorship, and/or publication of this article. The other authors (Tim Schutte, Marleen Kok, and Frans Opdam) declare no competing financial interests or non-financial interests, except from the review of the manuscript by Novartis, as part of the agreement between Novartis and the DRUP-trial investigators in accordance with the Drug Rediscovery Trial Protocol. No significant changes to the content of the manuscript were suggested. The suggested changes of Novartis and versions of the manuscript before and after their review are available upon reasonable request from the corresponding author.

Figures

Figure 1
Figure 1
Pictures of the patient described in case A: Upper left panel: erythematous maculopapular rash with (very) mild edema in the face an eyelids (not shown for privacy reasons) (photo taken on day 13 after start of alpelisib). Upper right panel: erythematous maculopapular rash of the left arm (photo taken on day 13). Central panels (day 6 after rechallenge, day 34 after initial start of alpelisib): Bulla of the left arm with erythema (central – left), bulla on back with erythema (central panel – right) and pubis (not shown). Assessment by dermatologist, most likely Bullous toxicoderma. Lower panel left: Peeling skin, or desquamation of left forearm with a white shade as a result of applied zinc ointment (day 6 after rechallenge) Lower panel right: some residue of peeling skin with underneath healed skin (day 14 after rechallenge).
Figure 2
Figure 2
Pictures of the patient described in case B: Panels A and B (9 days after initial start of alpelisib): erythematous maculopapular rash. Panel C: erythematous rash with mild edema in the face an eyelids (eyes not shown for privacy reasons) (photo taken the day after the second (clinical) rechallenge). Panel D: urticaria on left leg (photo taken the day after the second (clinical) rechallenge).
See this image and copyright information in PMC

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