Conversion from Positive to Negative EGFR Mutation due to Clonal Selection during Long-Term Treatment with Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors: A Case Report

Masatomo Ueda; Masashi Namba; Kentaro Tokumo; Tadashi Senoo; Wataru Okamoto; Masami Yamauchi; Noboru Hattori; Kazuhiko Sugiyama

doi:10.1159/000518246

Conversion from Positive to Negative EGFR Mutation due to Clonal Selection during Long-Term Treatment with Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors: A Case Report

Case Rep Oncol. 2021 Oct 18;14(3):1447-1453. doi: 10.1159/000518246. eCollection 2021 Sep-Dec.

Authors

Masatomo Ueda¹, Masashi Namba², Kentaro Tokumo², Tadashi Senoo³, Wataru Okamoto⁴, Masami Yamauchi², Noboru Hattori⁵, Kazuhiko Sugiyama^{2

4}

Affiliations

¹ Postgraduate Clinical Training Center, Hiroshima University Hospital, Hiroshima, Japan.
² Department of Clinical Oncology, Hiroshima University Hospital, Hiroshima, Japan.
³ Department of Respiratory Medicine, National Hospital Organization, Kure Medical Center, Hiroshima, Japan.
⁴ Cancer Treatment Center, Hiroshima University Hospital, Hiroshima, Japan.
⁵ Department of Respiratory Medicine, Hiroshima University Hospital, Hiroshima, Japan.

Abstract

A 77-year-old woman with postoperative recurrent non-small cell lung adenocarcinoma, which exhibited an epidermal growth factor receptor (EGFR) L858R mutation, was treated with gefitinib and erlotinib. Seven years after the start of treatment, the patient experienced a recurrence of malignant pleural effusion. However, 3 different genetic tests revealed that the lung adenocarcinoma cells in the pleural effusion had lost EGFR L858R mutation, suggesting that long-term treatment with EGFR-tyrosine kinase inhibitors (TKIs) converted EGFR mutation from positive to negative. The negative conversion of EGFR mutation as a mechanism of acquired resistance to EGFR-TKIs is considered rare and needs to be further investigated.

Keywords: Epidermal growth factor receptor mutation; Erlotinib; Gefitinib; Mechanisms of resistance; Non-small cell lung cancer.

Publication types

Case Reports