Lung adenocarcinoma with EGFR exon 19 insertion identified using a compact panel and its response to osimertinib: a case report.

1
Introduction
In Japan, several companion diagnostic tools are available for selecting molecular-targeted therapies. The mainstream approach at the time of initial treatment involves multicompanion diagnostics, which can simultaneously identify multiple gene mutations. Multicompanion diagnostics include the Lung Cancer Compact Panel® Dx (LCCP) and Oncomine™ Dx Target Test® (ODxTT) measured by next-generation sequencing (NGS), and AmoyDx® Lung Cancer Multi-Gene PCR Panel (AmoyDx) measured by polymerase chain reaction. Because each test detects or reports different types and numbers of gene variants, it is difficult to identify rare driver mutations.
Epidermal growth factor receptor (EGFR) exon 19 insertion (exon19ins) is an uncommon mutation that involves the insertion of 18 base pairs (six amino acids). The mutation is more common in women and non-smokers [1]. Exon19ins is rare among the uncommon mutations, accounting for only 0.6–1 % of all EGFR mutations [1,2].
Regarding the treatment of uncommon mutations, a pooled analysis of prospective studies using afatinib reported a progression-free survival (PFS) of 10.7 months and overall survival of 19.4 months [3]. Additionally, a phase II study of osimertinib showed an overall response rate of 50 % and PFS of 8.2 months [4]. However, exon19ins was not included in these studies, and treatment options for this specific mutation are not well established.
Herein, we report a case in which exon19ins diagnosed using LCCP responded to osimertinib treatment.

2
Case report
An 80-year-old man presented with chronic obstructive pulmonary disease secondary to smoking. The patient underwent left lower lobectomy with mediastinal lymph node dissection, which resulted in the pathological diagnosis of lung adenocarcinoma at stage T2aN0M0, stage IB (Union for International Cancer Control, 8th edition TNM). One year postoperatively, the patient underwent left pleurodesis with talc to treat malignant pleural effusion. Six months after pleurodesis, there was an increase in left pleural dissemination. The Oncomine Precision Assay, measured using NGS in clinical trials detected EGFR exon19ins in surgical specimens (Fig. 1). However, the ODxTT, a companion diagnostic test for EGFR mutations, did not report this mutation. Programmed cell death ligand 1 expression was 1–24 %. The patient was initially treated with carboplatin, pemetrexed, and pembrolizumab. After three courses of maintenance therapy, he developed malignant ascites and was hospitalized due to loss of appetite, with an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) 3.
Next, we tested LCCP, a companion diagnostic tool for EGFR mutations capable of detecting exon19ins. These results indicated the presence of an exon19ins. The patient was administered osimertinib, resumed adequate oral intake, and was discharged from the hospital.
One month after initiating osimertinib treatment, pleural dissemination and ascites were reduced (Fig. 2). However, the patient was hospitalized because of aspiration pneumonia. Despite successful antibiotic treatment, the patient remained hospitalized for palliative care. Osimertinib was discontinued and the patient received supportive care.

3
Discussion
As of April 2025, LCCP is the only multipanel test available for accurate detection of exon19ins during first-line treatment in Japan. However, ODxTT and AmoyDx did not report this mutation. The Cobas® EGFR Mutation Detection Kit v2.0 is a singleplex gene test and a companion diagnostic tool for EGFR mutations. However, this test erroneously identifies exon19ins as exon 19 deletion. LCCP can report a larger number of EGFR mutations than other companion diagnostic tools and help prevent rare EGFR mutations from being overlooked.
Currently, there is no established treatment protocol for exon19ins. Several case reports have documented the effectiveness of first- and second-generation EGFR tyrosine kinase inhibitors, with some cases showing responses lasting for over a year [1,5]. Osimertinib was occasionally administered to treat of exon19ins (Table 1) [[6], [7], [8], [9], [10]]. Previous reports have indicated that the best overall response to osimertinib often includes partial responses, with the treatment duration extending up to 16.8 months before discontinuation [6]. The efficacy of osimertinib was confirmed in this patient with poor ECOG-PS.
In conclusion, our findings reaffirm the efficacy of osimertinib against exon19ins. LCCP, which reports a wide range of EGFR mutations, is a valuable tool for identifying rare EGFR variants and guiding treatment decisions.

CRediT authorship contribution statement
Mika Horie: Conceptualization, Visualization, Writing – review & editing. Kazuhisa Nakashima: Supervision, Writing – review & editing. Kojiro Hata: Writing – review & editing. Yoshihiro Amano: Writing – review & editing. Mika Nakao: Writing – review & editing. Tamio Okimoto: Supervision, Writing – review & editing. Yukari Tsubata: Writing – review & editing. Takeshi Isobe: Writing – review & editing.

Consent for publication
Informed consent was obtained from the patient.

Funding
No funding was received.

Declaration of competing interest
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yukari Tsubata and Isobe Takeshi reports a relationship with AstraZeneca that includes: speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.