4446 - Effect of cumulative dose of maintenance temozolomide on overall survival in patients with high grade glia tumors: a single institution analysis

Background

Standard 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.

Methods

We 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.

Results

We 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 > = 4500 mg/m² versus 11 months when cumulative dose was < 4500 mg/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).

Conclusions

Our study shows that in patients with high grade glia tumors without MGMT hypermethylation a cumulative dose of maintenance TMZ < 4500 mg/m²negatively impacts on mOS compared to a cumulative dose of > = 4500 mg/m². Moreover time elapsed from diagnosis to beginning of treatment does not significantly influence mOS.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Department of Medical Oncology, ASST-Settelaghi, Varese (Italy).

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.