Extended cycles of adjuvant temozolomide improves survival outcomes in glioblastoma: a retrospective analysis

Abstract

Aim: Standard treatment includes post-surgical chemoradiotherapy and adjuvant temozolomide (TMZ) for glioblastoma (GBM). There is no consensus on the optimal duration for adjuvant TMZ. This study assessed whether prolonging adjuvant TMZ improved survival outcomes.

Methods: We retrospectively analyzed data of GBM patients who met inclusion criteria at our institute from September 2013 to December 2022. Patients who received 6 cycles of maintenance TMZ constituted the standard group, whereas those who underwent > 6 cycles were classified into the extended group. Kaplan-Meier method was used to estimate the median progression-free survival (PFS) and overall survival (OS). Independent predictors of OS and PFS were explored by Cox regression analyses.

Results: 100 patients were enrolled. Extended adjuvant TMZ significantly improved OS (28.0 vs. 10.0 months, P < 0.001) and PFS (22.0 vs. 8.0 months, P < 0.001) in newly diagnosed GBM patients. Subgroup analysis showed that patients with MGMT promoter methylation who received > 6 cycles of adjuvant TMZ experienced a significant increase in OS (34.0 vs. 9.0 months, P < 0.001) and PFS (26.0 vs. 9.0 months, P = 0.008). Additionally, in the extended group, patients with MGMT promoter methylation had better survival outcomes compared to MGMT promoter unmethylated patients (OS: 34.0 vs. 17.0 months, P = 0.013; PFS: 26.0 vs. 12.0 months, P = 0.025). In patients with solitary GBM, extended adjuvant TMZ resulted in better OS (11.0 vs. 32 months, P = 0.007) and PFS (9.0 vs. 24.0 months, P < 0.001). For patients with multiple GBM, undergoing six or more cycles of adjuvant TMZ did not significantly impact OS (P = 0.100) and PFS (P = 0.067). The Karnofsky Performance Status (KPS) is employed to assess the health condition of surgical patients. Patients with KPS > 70 exhibited better survival outcomes in the extended group. Nausea and vomiting were the main adverse events reported in both cohorts. However, fatigue emerged as the most severe side effect, specifically within the extended group.

Conclusion: This study indicated that prolonged adjuvant TMZ significantly enhanced OS and PFS in GBM, and the adverse events were acceptable. The benefits were particularly notable in those with MGMT promoter methylation, solitary GBM, and high KPS. The optimal cycles of adjuvant TMZ require large prospective studies to further validate and identify which patient groups benefit the most based on molecular subtyping and clinical characteristics.

Keywords

Glioblastoma / adjuvant temozolomide / MGMT promoter methylation / overall survival

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