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Acneiform eruptions with combination targeted cancer therapy in colorectal cancer patients

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Abstract

Purpose

Epidermal growth factor receptor inhibitors (EGFRI) can be used with pathway inhibitors, including mitogen-activated protein kinase kinase inhibitors (MEKIs), BRAF inhibitors (BRAFIs), and checkpoint inhibitors such as programmed death-ligand 1 (PD-L1) and programmed cell death protein 1 (PD-1) to treat colorectal cancer. These can precipitate treatment-resistant acneiform eruptions, prompting dose modification or discontinuation. Predicting the likelihood of severe rash development and crafting effective treatments may promote adherence to life-saving chemotherapy.

Methods

An Institutional Review Board-approved retrospective chart review of patients with colorectal cancer treated with EGFRI or MEKI in combination with HER2, BRAF, PI3K, or checkpoint inhibitors between January 1, 2016, and January 1, 2020, was performed. Surrogates for rash severity were investigated, including lower extremity involvement, utilization of oral steroids or retinoids, dose modification, and incidence of superinfection.

Results

Of 122 patients treated with combination therapy, 105 developed a rash, and 87 developed an acneiform eruption. Common combinations included MEKI/PD-LI, EGFRI/MEKI, and MEKI/PD-1I. Patients treated with EGFRI/MEKI developed the most severe rashes (p = 0.02). Lower extremity involvement was more frequent with EGFRI/MEKI compared to alternative combinations (p = 0.05). Drug holiday correlated with all rash severity surrogates, including rash grade, lower extremity involvement, oral steroid or retinoid use, and incidence of superinfection. Use of oral steroids or retinoids was associated with development of superinfection (p = 0.002). Prophylactic tetracycline use did not impact rash severity or rash incidence.

Conclusion

This is the first descriptive analysis to characterize acneiform eruptions for patients with colorectal cancer on combination cancer therapy. Approximately 85% of patients developed a cutaneous toxicity with what appears to be synergistic effects of EGFRI and MEKI combination therapy causing the most severe eruptions. Superinfection rate correlated to systemic therapy use beyond oral tetracyclines. Further investigation into the utility of prophylactic oral tetracyclines in this population is needed.

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Data availability

Available upon request to corresponding author.

Code availability

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Author information

Author notes

  1. Marina K. Ibraheim and Jonathan Lo contributed equally with this work.

Authors and Affiliations

  1. McGovern Medical School, Houston, USA

    Marina K. Ibraheim

  2. Baylor College of Medicine, Houston, USA

    Jonathan Lo & Rohit Gupta

  3. Department of Gastrointestinal Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, USA

    Christine Parseghian

  4. Department of Dermatology, University of Texas Health Science Center at Houston, Houston, USA

    Anisha B. Patel

  5. Department of Dermatology, University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1452, Houston, TX, 77030, USA

    Anisha B. Patel

Authors
  1. Marina K. Ibraheim
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  2. Jonathan Lo
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  3. Rohit Gupta
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  4. Christine Parseghian
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Contributions

Marina K. Ibraheim: investigation (equal), data curation (equal), writing original draft (equal), writing-review and editing (lead), and project administration (lead).

Jonathan Lo: investigation (equal), data curation (equal), and writing original draft (equal).

Rohit Gupta: investigation (equal), data curation (equal), and formal analysis (lead).

Christine Parseghian: conceptualization (equal) and writing-review and editing (equal).

Anisha B. Patel: conceptualization (equal), investigation (lead), methodology (lead), and writing-review and editing (equal).

Corresponding author

Correspondence to Anisha B. Patel.

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Ethics approval

Institutional IRB approved protocol PA15-0959.

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Waiver of consent obtained from institutional IRB.

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Not applicable—only aggregate data presented.

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The authors declare no competing interests.

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Ibraheim, M.K., Lo, J., Gupta, R. et al. Acneiform eruptions with combination targeted cancer therapy in colorectal cancer patients. Support Care Cancer 30, 8051–8058 (2022). https://doi.org/10.1007/s00520-022-07257-2

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  • DOI: https://doi.org/10.1007/s00520-022-07257-2

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