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Risk factor analysis for anti-epidermal growth factor receptor monoclonal antibody–induced skin toxicities in real-world metastatic colorectal cancer treatment

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Abstract

Purpose

Anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies are effective in treating RAS wild-type metastatic colorectal cancer (mCRC). However, their administration induces skin toxicity, markedly reducing patients’ quality of life. This study is aimed at identifying the risk factors associated with anti-EGFR monoclonal antibody-induced skin toxicities.

Methods

Patients with mCRC (n = 116) who received anti-EGFR monoclonal antibody treatment were retrospectively evaluated. Primary endpoint was evaluation of the risk factors for grade ≥ 2 overall skin toxicities during all the treatment periods. Furthermore, factors associated with each grade ≥ 2 skin symptoms were assessed.

Results

Incidence of total grade ≥ 2 skin toxicity symptoms was 61.2%, and those of grade ≥ 2 rash, dry skin, fissures, and paronychia were 34.5%, 25.9%, 20.7%, and 25.0%, respectively. Multivariate logistic regression analyses revealed that liver metastasis was an independent risk factor for overall grade ≥ 2 skin toxicities (adjusted odds ratio [OR], 2.88; 95% confidence interval [CI], 1.22–6.78; P = 0.02) and prophylactic administration of antibiotics as a preventive factor (OR 0.10; 95%CI 0.01–0.91; P = 0.04). For grade ≥ 2 rash, prophylactic use of systemic antibiotics and topical steroid ointment was a preventive factor (OR 0.37; 95%CI 0.16–0.89; P = 0.03). Moreover, liver metastasis (OR 8.37; 95%CI 1.98–35.47; P = 0.004) and prophylactic administration of antibiotics (OR 0.15; 95%CI 0.03–0.76; P = 0.02) were significantly associated with grade ≥ 2 paronychia.

Conclusion

Liver metastasis was suggested to be a risk factor for the incidence of overall grade ≥ 2 skin toxicities; moreover, preemptive systemic antibiotic administration drastically decreased this risk during all periods of anti-EGFR treatment for mCRC.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Author information

Authors and Affiliations

  1. Department of Clinical Pharmaceutics & Therapeutics, Faculty of Pharmaceutical Sciences, Hokkaido University of Science, 4-1, Maeda 7-jo 15-chome, Teine-ku, Sapporo, 006-8585, Japan

    Yoshitaka Saito

  2. Department of Pharmacy, Hokkaido University Hospital, Kita 14-jo, Nishi 5-chome, Kita-ku, Sapporo, 060-8648, Japan

    Yoshitaka Saito, Kazuki Uchiyama, Yoh Takekuma & Mitsuru Sugawara

  3. Cancer Center, Hokkaido University Hospital, Kita 14-jo, Nishi 5-chome, Kita-ku, Sapporo, 060-8648, Japan

    Yoshito Komatsu

  4. Laboratory of Pharmacokinetics, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo, Nishi 6-chome, Kita-ku, Sapporo, 060-0812, Japan

    Mitsuru Sugawara

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  1. Yoshitaka Saito
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Contributions

Participated in research design: YS, KU, and YK.

Conducted experiments: YS.

Performed data analysis: YS.

Drafting of the manuscript: YS.

All authors have read and approved the manuscript.

Corresponding author

Correspondence to Yoshitaka Saito.

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Ethical approval

All procedures performed in this study involving human participants were performed in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. For this type of study, the need for formal consent was waived by the Ethical Review Board for Life Science and Medical Research at Hokkaido University Hospital.

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Formal consent was not required for this type of study.

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Not applicable.

Conflict of interest

YS, KU, YT, and MS have no conflicts of interest. YK reports receiving grants and personal fees from Ono, TAIHO, CHUGAI, Eli Lilly, Yakult, Bristol-Myers, Merck, Takeda, Novartis, Bayer, and Daiichi-Sankyo and grants from Iqvia outside the submitted work.

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Saito, Y., Uchiyama, K., Takekuma, Y. et al. Risk factor analysis for anti-epidermal growth factor receptor monoclonal antibody–induced skin toxicities in real-world metastatic colorectal cancer treatment. Support Care Cancer 31, 504 (2023). https://doi.org/10.1007/s00520-023-07973-3

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