MON-086 - Treatment Duration of Temozolomide and Clinical Outcomes in Aggressive Pituitary Tumors and Pituitary Carcinomas: An Exploratory Retrospective Cohort Study

Background: Temozolomide (TMZ) is first-line treatment for aggressive pituitary tumors and pituitary carcinoma (APT/PC). However, the optimal duration of TMZ therapy remains uncertain. We evaluated the therapeutic effects of TMZ and compared prolonged vs shorter-term TMZ treatment in a large single-center cohort with long-term follow-up, encompassing a wide range of treatment durations, including up to 48 cycles.

Method: Patients with APT/PC treated with TMZ between 2015 and 2025 were included. Clinical, biochemical, radiological, pathological, treatment, and follow-up data were collected. Progression-free survival (PFS) was estimated using the Kaplan-Meier method and compared by the log-rank test. A 12-month landmark analyses were performed to evaluate the association between TMZ duration and PFS, thereby minimizing immortal time bias.

Results: A total of 53 patients with APT/PC were enrolled, including 6 with PC. The mean age at diagnosis was 34.2 ± 17.3 years, and 54.7% were male. Clinical subtypes included NFPA (n=21), ACTHoma (n=13), PRLoma (n=11), GHoma (n=7), and mixed GH/PRLoma (n=1). The median time from diagnosis to TMZ initiation was 8.3 years (IQR 5.0-12.9). Forty patients (75.5%) received TMZ alone, whereas 24.5% underwent concomitant TMZ and radiotherapy. The median number of TMZ cycles was 10 (IQR 6-18, range 2-48). During a median follow-up of 28.3 months (95% CI 20.5-41.5), the median PFS was 38.3 months (95% CI 26.6-not reached). At the last follow-up, partial regression, stable disease, and progressive disease (PD) were observed in 21 (39.6%), 15 (28.3%), and 17 (32.1%) patients; 3 functioning pituitary adenoma (FPA) achieved hormonal normalization despite residual disease. TMZ was discontinued for reasons other than PD in 22 patients, whereas 20 remained on treatment at the last follow-up. The TMZ cessation group showed a lower Ki-67 index, more frequent concurrent radiotherapy, and a higher rate of adverse events. In landmark analyses, neither continued TMZ treatment (vs cessation) nor prolonged treatment duration (≥12 vs < 12 cycles) was significantly associated with PFS (continued TMZ: HR 1.75, 95% CI 0.54-5.65; P = 0.35; TMZ cycles ≥12: HR 1.09, 95% CI 0.92-3.42; P = 0.89). Seven patients received more than 24 TMZ cycles. Among them, 3 experienced PD, 1 developed grade 1 leukopenia, and 2 reported gastrointestinal symptoms. Among other potential factors influencing PFS, no significant differences were observed according to clinical subtype (NFPA vs FPA) or Ki-67 (≥3% vs < 3%). Concurrent chemoradiotherapy showed a nonsignificant trend toward a lower risk of progression compared with TMZ alone (HR 0.26, 95% CI 0.06-1.13; P = 0.073).

Conclusion: TMZ was effective in APT/PC treatment. No significant association was observed between prolonged treatment duration and prognosis. Further large-scale studies with adequate control of confounding factors are needed.

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