Temozolomide in Aggressive Pituitary Tumors and Metastatic PitNETs: A Brazilian Multicenter Real-World Cohort Study

Purpose To evaluate the real-world efficacy and safety of temozolomide (TMZ) in aggressive and metastatic pituitary neuroendocrine tumors (PitNETs) in a Latin American setting, addressing whether TMZ achieves meaningful radiological and biochemical disease control with acceptable toxicity. Methods We conducted a retrospective multicenter study across Brazilian reference centers including patients with aggressive/metastatic PitNETs treated with TMZ and followed for ≥ 6 months. Radiological response was assessed using RECIST 1.1. For functioning PitNETs, biochemical response was assessed using prespecified hormonal criteria. Adverse events were collected from medical records. Results Thirty patients were included (mean age 29.5 years; 53% female). All tumors were macroadenomas and 56% were giant (> 4 cm). Twenty-one PitNETs were functioning and four were metastatic. Ki-67 was > 3% in 73% of cases. Median time from diagnosis to TMZ initiation was 100 months. Radiological disease control rate (partial response or stable disease) was 96.7%. Among functioning tumors, biochemical disease control rate was 81.3%, with an objective biochemical response rate (complete + partial response) of 68.8%. Adverse events occurred in 66% of patients, most commonly nausea and myelotoxicity. Conclusion In this multicenter Brazilian real-world cohort, TMZ provided high radiological and biochemical disease control with an acceptable safety profile, supporting TMZ as preferred first-line systemic chemotherapy for aggressive/metastatic PitNETs after failure of standard therapies.