Temozolomide in aggressive and metastatic pituitary tumors: a Brazilian multicenter real-world cohort study

To evaluate the real-world efficacy and safety of temozolomide (TMZ) in aggressive and metastatic pituitary neuroendocrine tumors in a Latin American setting, and to address whether TMZ achieves meaningful radiological and biochemical disease control with acceptable toxicity. We conducted a retrospective multicenter study across Brazilian reference centers including patients with aggressive/metastatic pituitary adenomas treated with TMZ and followed for ≥ 6 months. The radiological response was assessed via RECIST 1.1. For functioning pituitary adenomas, biochemical response was assessed using prespecified hormonal criteria. Adverse events were collected from medical records. Thirty patients were included (mean age 29.5 years; 53% female). All the tumors were macroadenomas, and 56% were giant (> 4 cm). Twenty-one pituitary adenomas were functioning and four were metastatic. Ki-67 was > 3% in 73% of the patients. The mean time from diagnosis to TMZ initiation was 102 months. The radiological disease control rate (partial response or stable disease) was 93.3%. Among functioning tumors, the biochemical disease control rate was 81.2%, with an objective biochemical response rate (complete + partial response) of 68.8%. Adverse events, most commonly nausea and myelotoxicity, occurred in 66% of patients. In this multicenter Brazilian real-world cohort, TMZ provided high radiological and biochemical disease control with an acceptable safety profile, suggesting that TMZ is the preferred first-line systemic chemotherapy for aggressive/metastatic pituitary adenomas after the failure of standard therapies.