Challenges associated with the treatment of E709K and L858R double mutation in lung adenocarcinoma: A case report and literature review

Non-small-cell lung cancer (NSCLC) frequently harbors EGFR mutations, with the L858R and exon 19 deletions being the most prevalent. Rare EGFR exon 18 mutations, such as E709K, account for a small proportion but may significantly influence treatment response. The coexistence of E709K and L858R mutations presents unique therapeutic challenges and opportunities. This report describes a 64-year-old Chinese woman diagnosed with advanced lung adenocarcinoma harboring concurrent EGFR mutations (exon 18 p.E709K and exon 21 p.L858R). Initial treatment with osimertinib achieved partial response with a progression-free survival of 8 months, followed by disease progression. The patient was subsequently treated with afatinib, which showed transient efficacy but was discontinued due to poor tolerance. Combination therapies involving chemotherapy (paclitaxel-platinum and pemetrexed), bevacizumab, radiotherapy and the third-generation EGFR TKI amitinib were sequentially administered, resulting in sustained symptomatic relief and clinical benefit. Leptomeningeal metastasis was later managed with intrathecal pemetrexed and ongoing amitinib therapy. In conclusion, this case highlights the complex clinical course of NSCLC with dual EGFR mutations, including E709K. While first- and second-generation TKIs offer variable efficacy, third-generation TKIs like amitinib may provide a durable benefit in selected patients. Comprehensive genomic profiling and individualized therapeutic strategies are essential for optimizing outcomes, particularly in cases involving rare EGFR mutations.