417P - Effect of cumulative dose of maintenance temozolomide on overall survival in patients with high grade glia tumours: A single institution analysis

Abstract

BackgroundStandard of care of high grade glia tumors is represented by concomitant temozolomide (TMZ) and radiotherapy (RT), followed by maintenance TMZ. In clinical practice, administering the full programmed cumulative dose of treatment is often a challenge. The effect of different cumulative doses of maintenance TMZ on median overall survival (mOS) is yet not known. MethodsWe retrospectively analyzed patients with histological diagnosis of high grade glia tumors (91% grade IV, 7% grade III, 2% others) treated at our institution with RT plus concomitant TMZ, followed by maintenance TMZ (according to the trial by Stupp et al.), between February 2012 and April 2019. We planned 6 cycles of maintenance TMZ in patients without MGMT hypermethylation and 12 cycles in those with MGMT hypermethylation. The main objective of our research was to study the effect of cumulative dose of maintenance TMZ on mOS in patients without MGMT hypermethylation. We also focused on time from diagnosis to beginning of chemoradiotherapy and its potential effect on mOS in our whole cohort. We performed statistical analysis with SPSS, using Kaplan-Meier curves. ResultsWe enrolled 114 patients, with median age of 63 years (IQR 54-69 y). MGMT was hypermethylated in 35 (30%) patients, not hypermethylated in 56 (49%) patients, unknown in 24 (21%) patients. In our cohort, mOS was 14 months, in line with previously reported data. In patients without MGMT hypermethylation, mOS was 23,4 months when cumulative dose of maintenance TMZ was>= 4500mg/m2 versus 11 months when cumulative dose was < 4500mg/m2(HR 0,23 [0,10-0,54, CI 95%], p<0,001). When considering our entire cohort, chemoradiotherapy was started in a median of 44 days from diagnosis (IQR 35-56 days); mOS was not statistically different in patients who started therapy over 42 days after diagnosis (HR 0,76 [0,44-1,33, CI 95%], p 0,35). ConclusionsOur study shows that in patients with high grade glia tumors without MGMT hypermethylation a cumulative dose of maintenance TMZ < 4500mg/m2negatively impacts on mOS compared to a cumulative dose of>= 4500mg/m2. Moreover time elapsed from diagnosis to beginning of treatment does not significantly influence mOS. Legal entity responsible for the studyDepartment of Medical Oncology, ASST-Settelaghi, Varese (Italy). FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.