Clinical outcomes and safety of central nervous system tumor patients in phase 1 trials: A single-institution experience.

Abstract

e14047 Background: Central nervous system (CNS) tumors present unique therapeutic challenges due to limited drug penetration across the blood-brain barrier and the potential for neurologic toxicity. Historically CNS tumors have been underrepresented in early-phase clinical trials (CTs), limiting the data related to safety and efficacy of investigational therapies in this patient population. Methods: A retrospective study of patients with primary CNS tumors enrolled in phase 1 CTs was conducted at Miami Cancer Institute, between January 2018 and October 2024, included baseline demographic, clinical, treatment, and laboratory data. Outcomes assessed included overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related toxicities. Survival outcomes were evaluated using Kaplan-Meier estimates and Cox proportional hazards models. Results: A total of 46 patients with primary CNS tumors were enrolled in phase 1 trials (median age 53 years; 54.3% female; 43.5% non-Hispanic White). Most patients had KPS ≥80 (82.6%). Patients received targeted therapy alone (47.8%) or combination regimens (52.2%), with a median of 3.5 cycles administered (IQR, 2–8). Concomitant anti-epileptic drugs and steroids were used in 67.4% and 73.9% of patients, respectively. The ORR was 15.2% and DCR was 58.7%. Median PFS was 3.7 months (95% CI, 2.8–5.5) and median OS was 11.0 months (95% CI, 8.2–14.3). OS was shorter for KPS <80 vs ≥80 (5.3 vs 12.6 months; p=0.041). On multivariable analysis, ≥2 prior systemic therapy lines (HR 104.76; 95% CI, 7.71–1423.17; p<0.001) and concurrent steroid use (HR 15.61; 95% CI, 1.30–186.97; p=0.030) were associated with higher mortality. Grade 3-4 adverse events occurred in 69.6%. No treatment-related deaths were reported. Conclusions: Patients with primary CNS tumors can derive meaningful clinical benefit from participation in phase 1 trials. Survival outcomes were comparable to patients with other tumor types treated at our center during the same time frame. Baseline functional status, prior therapy exposure, and the need for concurrent steroids appear to identify higher-risk patients. These findings support continued and expanded inclusion of primary CNS tumor populations in phase 1 trials. Efficacy outcomes of all patients (n=46). Outcome/Metric Estimates PFS Median, months, (95% CI)6-month rate, %12-month rate, %24-month rate, % 3.7 (2.8-5.5)53.3 (40.6-70.1)25.5 (15.4-42.3)9.3 (3.7-23.5) OSMedian, months, (95% CI)6-month rate, %12-month rate, %24-month rate, % 11.0 (8.2-14.3)72.4 (60.2-87.0)46.9 (33.7-65.2)NA