Abstract Disclosure: C.R. de Macedo: None. I.P. de Magalhães: None. A. Glezer: None. M. Berardo Carneiro da Cunha Neto: None. N.R. de Castro Musolino: None. O. Feher: None. R.L. Batista: None. Introduction: Temozolomide (TMZ) is an oral alkylating agent used in management of glioblastoma multiforme. Since 2006, TMZ is used in patients with pituitary tumors (PITNets) with yielded promising outcomes as an alternative for aggressive PITNets. Objective: To evaluate the response to TMZ in patients with aggressive or metastatic PITNets within the largest tertiary oncology service in Latin America. Patients and Methods: We screened all cases that received TMZ at our institution between 2008-2023 (n=661, primarily glioblastoma cases). We identified 7 cases that TMZ was employed for treating PITNets. We assessed for PITNet characteristics, functionality, timelines of treatment initiation, correlation with radiotherapy, duration of TMZ usage and treatment response utilizing the RECIST criteria. Results: At the time of diagnosis, all patients presented with macro-PITNets and 6 were giant (size greater than 4 cm). In terms of hormonal production, 4 cases were prolactinomas and 3 were non-functioning PITNets. Over the follow-up period, these tumors exhibited an aggressive behavior, manifesting rapid tumor growth despite optimized treatments and one case was recategorized as metastatic PitNET. All cases demonstrated a Ki-67 index greater than or equal to 3%. The initiation of TMZ occurred on average 9.48 years after diagnosis and subsequent to multiple surgical interventions (average of 1.8 surgeries). In 5 cases, TMZ followed radiotherapy. Among the cohort, 3 of 7 patients underwent 6 cycles of TMZ, one underwent 5 cycles, another had an extended treatment of 10 cycles and 2 patients received only 3 cycles due to adverse effects. In terms of treatment response, 4 patients exhibited stable disease, one achieved a partial response (PR) and 2 had disease progression. The most commonly side effect was mild nausea and vomiting and one patient required dose adjustment due to thrombocytopenia. A second course of TMZ was warranted in 2 cases that previously demonstrated a PR (on average one year after the initial treatment). While one case sustained the PR, the other experienced disease progression. Conclusion: The administration of this treatment was often postponed, potentially attributed to the significant disparities in opinions regarding the optimal timing of treatment initiation and the most suitable duration of usage. However, TMZ demonstrated its efficacy in maintaining disease stability for the majority of cases, with good tolerability and safety, even when used later, after multiple surgical procedures, and in patients with high Ki67 levels. Presentation: 6/2/2024