Advanced lung adenocarcinoma with rare EGFR exon 21 T854A mutation: a case report on increased dose osimertinib following resistance

<i>EGFR</i> T854A mutation, a rare genetic alteration, presents challenges in the treatment of lung adenocarcinoma due to its potential role in drug resistance. This case describes a 67-year-old male patient who was diagnosed with advanced left lower lobe adenocarcinoma with <i>EGFR</i> exon 21 L858R mutation and <i>EGFR</i> amplification in January 2018. Subsequently, the patient started gefitinib treatment, and 3 months later, the treatment effect assessment showed a partial response (PR) at regular follow-up according to RECIST evaluation criteria. Efficacy was maintained as PR/SD up to January 2021 until disease progression (PD). At the same time, the second genetic test showed that in addition to <i>EGFR</i> exon 21 L858R, there was also a new and rare <i>EGFR</i> exon 21 T854A mutation. In response, Osimertinib treatment was started in February 2021, and 3 months later, CT scans showed tumor shrinkage and stable disease (SD) that continued until September 2022. However, in December 2022, the enlargement of the primary tumor and the emergence of new metastases once again suggested disease progression after drug resistance. We implemented a double dose of Osimertinib treatment strategy for the patient. The patient achieved disease control and maintained progression-free survival for nearly 9 months without exhibiting any dose-related hematological or other systemic toxicities. Another progression of the disease occurred in September 2023, and newer drug-resistant mutations such as <i>EGFR</i> exon 20 C797S and exon 21 V834L appeared. Furthermore, we adopted double Osimertinib combined with Cabozantinib therapy. Two months later, imaging examination showed that the lesions in various parts of the body were stable. Except for dryness of oral and nasal mucosa, the patient did not experience other serious adverse reactions.