Osimertinib with chemotherapy in advanced non-small cell lung cancer with vaginal metastasis harboring EGFR exon 21 L858R and NTRK1 exon 16 V679M mutations: a case report with prolonged progression-free survival.

BACKGROUND

In recent years, significant progress has been achieved in the treatment of non-small cell lung cancer (NSCLC). The emergence of gene sequencing technology has revolutionized the management of patients with driver gene mutations, offering substantial survival benefits to patients with actionable oncogenic mutations. Epidermal growth factor receptor (EGFR) mutations are one of the most common driver mutations in NSCLC patients, while neurotrophic tyrosine kinase (NTRK) mutations are rare; co-mutations are extremely uncommon. NSCLC frequently disseminates to the brain and bone, with vaginal metastasis being exceptional. Here, we report the first case of vaginal metastasis from NSCLC featuring co-mutations of EGFR and NTRK1, in which a progression-free survival (PFS) of 14 months was achieved through the combination of osimertinib and chemotherapy.

CASE DESCRIPTION: We present a case of 54-year-old non-smoking woman with a history of uterine fibroids (total hysterectomy in 2008) and depression (on mirtazapine). She underwent left upper lobectomy for lung adenocarcinoma (LUAD) (pathological stage: pT2N0M0) in 2020, with no recurrence observed after the lobectomy. In January 2024, she was initially diagnosed with a vaginal tumor due to intermittent vaginal bleeding for four months following intercourse. She received two cycles of neoadjuvant chemotherapy (carboplatin 577 mg + paclitaxel 259 mg), achieving a partial response (PR). In March 2024, she underwent radical surgery and postoperative pathological examination confirmed that the vaginal tumor originated from lung cancer. Next-generation sequencing (NGS) revealed co-mutations in EGFR exon 21 L858R and NTRK1 exon 16 V679M, consistent with stage IV disease. Subsequently, the patient received two cycles of postoperative carboplatin-paclitaxel chemotherapy, but discontinued due to hypoleukocytosis. In June 2024, she initiated osimertinib (80 mg/day); no osimertinib-related adverse reactions were observed. As of June 2025, she has achieved 14 months of PFS, with vaginal bleeding resolved and no recurrence.

CONCLUSIONS

In patients with a history of lung cancer presenting with a vaginal mass, the possibility of vaginal metastasis from lung cancer should be carefully evaluated and advanced diagnostic methods such as NGS are recommended. This case highlights the advantages of comprehensive NGS followed by chemotherapy and osimertinib in managing NSCLC with vaginal metastasis and EGFR/NTRK1 co-mutations.