Dermatologic adverse events related to the PI3Kα inhibitor alpelisib (BYL719) in patients with breast cancer



Rash develops in approximately 50% of patients receiving alpelisib for breast cancer, often requiring dose modifications. Here, we describe the clinicopathologic, laboratory, and management characteristics of alpelisib-related dermatologic adverse events (dAEs).


A single center-retrospective analysis was conducted. Data were abstracted from electronic medical records.


A total of 102 patients (mean age 56 years, range 27–83) receiving alpelisib most frequently in combination with endocrine therapy (79, 77.5%) were included. We identified 41 (40.2%) patients with all-grade rash distributed primarily along the trunk (78%) and extremities (70%) that developed approximately within two weeks of treatment initiation (mean 12.8 ± 1.5 days) and lasted one-week (mean duration 7.1 ± 0.8 days). Of 29 patients with documented morphology of alpelisib-related dAEs, 26 (89.7%) had maculopapular rash. Histology showed perivascular and interface lymphocytic dermatitis. All-grade rash correlated with an increase in serum eosinophils from 2.7 to 4.4%, p < 0.05, and prophylaxis with non-sedating antihistamines (n = 43) was correlated with a reduction of grade 1/2 rash (OR 0.39, p = 0.09). Sixteen (84.2%) of 19 patients with grade 3 dAEs resulted in interruption of alpelisib, which were managed with antihistamines, topical and systemic corticosteroids. We did not observe rash recurrence in 12 (75%) patients who were re-challenged.


A maculopapular rash associated with increased blood eosinophils occurs frequently with alpelisib. While grade 3 rash leads to alpelisib therapy interruption, dermatologic improvement is evident with systemic corticosteroids; and most patients can continue oncologic treatment at a maintained or reduced dose upon re-challenge with alpelisib.

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Alanine aminotransferase




Complete blood count


Common Terminology Criteria for Adverse Events


Dermatologic adverse events


Drug reaction with eosinophilia and systemic symptoms


Epidermal growth factor receptor


Electronic medical record




Human epidermal growth factor receptor-2


Human epidermal growth factor receptor-3


Hormone receptor


Monoclonal antibody


Mitogen-activated protein kinase enzyme


Odds ratio




Phosphatidylinositol-4,5-phosphate-3-kinase alpha catalytic subunit


Phosphatase and tensin homolog


Receptor tyrosine kinase


Standard error mean


Selective estrogen receptor degrader


Selective estrogen receptor modulator


Stevens–Johnson syndrome/toxic epidermal necrolysis


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The authors thank the patients and staff at Memorial Sloan Kettering Cancer Center.


This work was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748. DGW is supported by a Medical Scientist Training Program grant from the NIH (T32GM007739) to the Weill Cornell/Rockefeller/Sloan-Kettering Tri-Institutional MD-PhD Program.

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Correspondence to Mario E. Lacouture.

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Conflict of interest

DGW declares no conflicts of interest. DMB declares no conflicts of interest. VSB declares consulting/advisory agreements with Pfizer and Anthem Foundation. VSB receives research funding from the NIH (5 R37 CA214785). JFB declares no conflicts of interest. PRD declares no conflicts of interest. SAF receives research funding from Genentech/Roche, AstraZeneca, and Decibel Therapeutics. SAF has stock/equity ownership in Urogen Pharma, Allogene Therapeutics, Kronos Bio, Vida Ventures, Kite Pharma, and Neogene Therapeutics. KLJ declares consulting/advisory board roles with Novartis, Spectrum Pharmaceuticals, ADC Therapeutics, Pfizer, BMS, Abbvie, AstraZeneca, Jounce Therapeutics, Taiho, Oncology, Genentech, Synthon, Lilly Pharmaceuticals, and Intellisphere. KLJ receives research funding from Novartis, Clovis Oncology, Genentech, Astra Zeneca, ADC Therapeutics, Novita Pharmaceuticals, Debio Pharmaceuticals, Pfizer, Lilly Pharmaceuticals, Zymeworks, Immunomedics, and Puma Biotechnology. DEL declares no conflicts of interest. TL declares no conflicts of interest. SM declares consulting/advisory agreements with Daiichi Sankyo, Carrick, Eli Lilly, Genentech, MacroGenics, and GSK Speakers Bureau Genetech. SM receives research support from Novartis, Genentech, Astra Zeneca/ MedImmune, Seattle Genetics, and Daiichi Sankyo. PR declares a consulting/advisory agreement with Novartis. PR receives institutional research support from Illumina and GRAIL. MS is an employee of Novartis. TAT declares consulting/advisory agreements with Genentech/Roche, Pfizer, AstraZeneca, Merck, Puma, Advaxis, Celgene, Innocrin, Genomic Health, Bristol-Myers Squibb, Samsung, Athenex, Aduro Biotech, Halozyme, Daiichi Sankyo, Ionis. TT receives research funding from Eisai, Pfizer, Novartis, Innocrin, AstraZeneca, Astellas, Immunomedics, Genentech, Daiichi, and Carrick. LTV declares no conflicts of interest. MEL declares a consulting/advisory agreement with Novartis.

Ethical approval

Our retrospective research study was approved by and in accordance with the ethical standards of Memorial Sloan Kettering Cancer Center’s Institutional Review Board committee (Protocol # 16-458). This article does not contain any studies with human or animals performed by any of the authors.

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Wang, D.G., Barrios, D.M., Blinder, V.S. et al. Dermatologic adverse events related to the PI3Kα inhibitor alpelisib (BYL719) in patients with breast cancer. Breast Cancer Res Treat (2020).

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  • Alpelisib
  • BYL719
  • Rash
  • PI3K
  • PIK3CA
  • Adverse event