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Successful treatment of an osimertinib-resistant lung adenocarcinoma with an exon 18 EGFR mutation (G719S) with afatinib plus bevacizumab

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Summary

Exon 18 mutations account for only 3.6% of EGFR mutations, and tumors with exon 18 mutations are often unresponsive to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). We present a novel case of a lung adenocarcinoma with an exon 18 mutation resulting in a glycine to serine substitution at position 719 of the EGFR protein. The patient received osimertinib, a third generation EGFR-TKI, as the first-line treatment, but the disease progressed during treatment. Analysis of circulating free DNAs via next generation sequencing revealed TP53 mutations and EGFR and MET amplifications, as well as the exon 18 mutation. On the basis of these results, we administered afatinib, a second-generation TKI, and bevacizumab, a vascular endothelial growth factor inhibitor, as the second-line treatment. The patient’s symptoms improved, and this treatment was continued for 12 months. This report suggests that afatinib plus bevacizumab can effectively treat osimertinib-refractory lung tumors with an exon 18 mutation.

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Acknowledgments

Thank you for the patient and families, and we appreciated to the Lung Cancer Genomic Screening Project for Individualized Medicine in Japan.

Funding

The authors did not receive any funding for this study.

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Authors and Affiliations

  1. Department of Thoracic Oncology, Osaka Prefectural Hospital Organization, Osaka International Cancer Institute, Otemae 3-1-69, Chuo-ku, Osaka City, Osaka, 541-8567, Japan

    Motohiro Tamiya, Kei Kunimasa, Kazumi Nishino, Hayato Kawachi, Kika Kuno, Takako Inoue, Hanako Kuhara, Fumio Imamura & Toru Kumagai

  2. Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwanoha 6-5-1, Kashiwa City, Chiba, 277-8577, Japan

    Shingo Matsumoto & Koichi Goto

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  1. Motohiro Tamiya
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  2. Kei Kunimasa
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Contributions

Motohiro Tamiya designed the study and wrote the initial draft of the manuscript. Shingo Matsumoto and Koichi Matsumoto contributed to analysis the cfDNA by Guardant360. Kei Kunimasa assisted in the preparation of the manuscript. All other authors have contributed to review the manuscript. All authors approved the version of the manuscript finally and agree to be accountable for all aspects of the work.

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Correspondence to Motohiro Tamiya.

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Conflict of interest

Motohiro Tamiya has lecture fee from AstraZeneca and Boehringer Ingelheim and other authors have no conflicts of interest to declare under consideration for publication.

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Institutional review board (IRB) approval for this study was obtained from the Medical Research Ethics Committee of Osaka International Cancer Institute.

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Waived by the IRB because of the retrospective nature of this case report. However, we got the informed consent of analyzing the cfDNA byGuardant360.

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Tamiya, M., Kunimasa, K., Nishino, K. et al. Successful treatment of an osimertinib-resistant lung adenocarcinoma with an exon 18 EGFR mutation (G719S) with afatinib plus bevacizumab. Invest New Drugs 39, 232–236 (2021). https://doi.org/10.1007/s10637-020-00966-7

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