Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) by osimertinib and continued treatment with dose reduction for postoperative recurrence of lung adenocarcinoma: a case report.

Background: Osimertinib is the standard third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) of choice for EGFR mutation-positive non-small cell lung cancer. Its major adverse effects include diarrhea and skin symptoms, although syndrome of inappropriate secretion of antidiuretic hormone (SIADH) has been reported as a rare event. In previous reports, patients were switched to another drug after the onset of SIADH. We report the first case of osimertinib-induced SIADH in a patient with lung adenocarcinoma with an EGFR T790M mutation, with, therefore, no effective therapeutic alternative, where the patient was able to resume treatment at a reduced dose without recurrence of SIADH. Case Description: An 80-year-old man with a history of hypertension, diabetes mellitus, and partial right nephrectomy for right renal cell carcinoma, but with preserved renal function, underwent thoracoscopic left upper lobectomy in 2013 for lung adenocarcinoma with the EGFR mutation of exon 19 deletion. He was administered gefitinib for multiple postoperative recurrent lung metastases in 2017. However, since a right lower lobe nodule continued to grow and a biopsy confirmed the presence of the resistant mutation of Exon 20 T790M, we administered 80 mg/day osimertinib in 2022, with subsequent shrinkage of the metastases. Seven months later, the patient developed hyponatremia. Evaluation confirmed SIADH diagnosis, and without lung cancer progression, osimertinib-induced SIADH was suspected. Hence, we discontinued osimertinib and initiated saline infusion, oral sodium chloride, and water restriction, which led to normalization of serum sodium levels by day 14. One month later, osimertinib 80 mg/day was resumed; however, two months later, hyponatremia recurred, necessitating discontinuation of osimertinib and initiation of water restriction and oral sodium chloride therapy. Five days later, serum sodium normalized. Based on his clinical course, the cause of SIADH was attributed to osimertinib. Osimertinib was then restarted at 40 mg/day, without recurrence of SIADH. At 18 months after dose reduction, there has been no growth of the pulmonary metastases. Conclusions: This case suggests that osimertinib treatment can be continued with dose reduction in lung adenocarcinoma patients who develop SIADH, especially when alternative treatment options are limited.