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Rare ocular toxicity induced by pertuzumab/QL1209 in healthy chinese subjects: case reports and whole-exome sequencing analysis

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Summary

Pertuzumab is a recombinant anti-HER2 humanized monoclonal antibody widely used for the adjuvant treatment of HER2-positive breast cancer. Its safety is well established with the most common adverse effects being diarrhea and rash. To our knowledge, severe pertuzumab-induced ocular adverse events have never been reported. Herein, we describe several cases of pertuzumab/QL1209 (pertuzumab biosimilar)-induced blurred vision in healthy Chinese male subjects after a single injection of 420 mg pertuzumab/QL1209. Persistent optic nerve damage and vision loss occurred in the most severe case even after ophthalmic treatment. We conducted whole-exome sequencing (WES) of DNA samples from 5 cases and 13 controls to analyze the potential genetic factors and identified some associated variants (rs80303690 in RBM24, rs117375173 in CASR, rs1805097 in IRS2, and rs1227049 in CDH23). Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Gene Ontology (GO) terms gene enrichment analyses were carried out for differentially expressed genes clustered in the PI3K/AKT/mTOR and Ras/Raf/MAPK signaling pathways, which were exactly activated by HER2 phosphorylation. In summary, this is the first report describing the occurrence of ocular toxicity induced by pertuzumab in the Chinese population and exploring the possible genetic mechanisms. These findings could provide evidence for clinicians to raise concerns about the risk of ocular toxicity with the clinical use of pertuzumab.

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Acknowledgements

The authors wish to thank the patient in this study.

Funding

This work was supported by National Natural Science Foundation of China (No. 81803639); Hunan Provincial Natural Science Foundation of China(No. 2020JJ5852); the Key Research and Development Project of Hunan Province (2020SK2010).

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Authors and Affiliations

  1. Center of Clinical Pharmacology, Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China

    Junlong Ma, Wenjing Chen, Zhanqing Hu, Jie Huang, Chengxian Guo, Chan Zou & Guoping Yang

  2. Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410013, Hunan, China

    Guoping Yang

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  1. Junlong Ma
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  2. Wenjing Chen
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  3. Zhanqing Hu
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  4. Jie Huang
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Contributions

JM and WC collected and interpreted the data. ZH, JH and CG performed the experiments. JM and CZ prepared the original draft of the manuscript. CZ and GY conceived and designed the study. All authors contributed to the article and approved the submitted version.

Corresponding authors

Correspondence to Chan Zou or Guoping Yang.

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Approval for the study was obtained from the Ethical Committee of Third Xiangya Hospital, Central South University. Informed consent was provided according to the Declaration of Helsinki. The patients provided their written informed consent to participate in this study.

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Informed consent was obtained from the patient.

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Authors declare no conflicts of interest for this study.

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Ma, J., Chen, W., Hu, Z. et al. Rare ocular toxicity induced by pertuzumab/QL1209 in healthy chinese subjects: case reports and whole-exome sequencing analysis. Invest New Drugs 40, 861–867 (2022). https://doi.org/10.1007/s10637-022-01256-0

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