Abstract 374P
Background
No standard of care after Stupp protocol for high grade glioma exists. Prospective (RESCUE trial) and retrospective studies have shown that TMZ rechallenge, either standard (S-TMZ) or dose-dense (D-TMZ) regimens, could be an option for patients with treatment free-interval (TFI) > 2mo after Stupp. IDH1 mutant (mut) and patients with grade 3 tumors could specially benefit from TMZ rechallenge.
Methods
VHIO institutional database was queried for treatment history and outcomes in pts with WHO grade III-IV glioma with TFI > 3 mo between January 2010 and April 2020. Second line progression free survival (PFS) was estimated using Kaplan-Meier methods.
Results
N=39 pts were identified. Majority of pts had grade 4 WHO gliomas (n=31; 79.5%). IDH1 status was available for 30 pts; with 4 pts (13.3%) having IDH1 mut. Most underwent complete (n=10; 25.6%) or partial (n=23; 59%) resection. All pts completed Stupp protocol and had a median TFI of 11.3mo (CI95% 8.3-15.0). N=33 pts (84.6%) were retreated with TMZ (82% with S-TMZ and 18% with D-TMZ) while. N=6 pts (15.6%) received other treatments (OTHER), including Bevacizumab in 10% and clinical trials in 2.5%. Having TFI > 11 mo (p=0.05) and being younger than ≤65 years (p=0.03) were associated with increased PFS, but neither IDH1 mut status nor grade were prognostic. Median PFS was longer in pts receiving TMZ (S-TMZ and D-TMZ) than OTHER options (5.4 vs 2.9 mo; HR 0.4, p=0.08). Because there was a bias towards TMZ use in patients with longer TFI (TMZ use 49% in TFI <11mo vs 95% in over TFI>11mo) we compared outcomes only in patients with TFI between 3 and 11 months. The D-TMZ group had longer median PFS compared to OTHER (11.58 vs 2.94 mo; HR=4.1, p=0.03). In its with TFI>11 mo, median PFS with S-TMZ rechallenge was 7.62 mo. Pts with response to 2L had longer previous TFI (18 vs 9 mo; p=0,05) and PFS to Stupp protocol (27,6 vs 18,6 mo; p=0,1 - not significant).
Conclusions
TMZ rechallenge is a feasible option for pts with high grade glioma with TFI > 3 mo, with D-TMZ having improved outcomes in selected pmts with short TFI. Although prospective studies and larger number of pts are needed; younger pts, and those with long TFI > 11 mo seem to have better outcomes with TMZ.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
M. Gonzalez: Advisory/Consultancy: Roche; Travel/Accommodation/Expenses: Astellas, Bayer and Pand Lilly. R. Dienstmann: Advisory/Consultancy: Roche, Boehringer Ingelheim; Speaker Bureau/Expert testimony: Roche, Ipsen, Amgen, Servier, Sanofi, Merck Sharp and Dohme; Research grant/Funding (self), Research grant/Funding (institution): Merck, Pierre Fabre. J. Carles: Advisory/Consultancy: Bayer Johnson & Johnson Bristol-Myers Squibb Astellas Pharma Pfizer Sanofi MSD Oncology Roche AstraZeneca; Speaker Bureau/Expert testimony: Bayer Johnson & Johnson Asofarma Astellas Pharma; Travel/Accommodation/Expenses: BMS, Ipsen, Roche, AstraZeneca; Research grant/Funding (institution): AB Science, Aragon Pharmaceuticals, Arog Pharmaceuticals, INC, Astellas Pharma., Astrazeneca AB, Aveo Pharmaceuticals INC, Bayer AG, Blueprint Medicines Corporation, BN Immunotherapeutics INC, Boehringer Ingelheim España, S.A., Bristol-Myers Squibb Intern. M. Vieito Villar: Advisory/Consultancy: Debio, Roche, TFS; Travel/Accommodation/Expenses: Roche, Merck-Serono. All other authors have declared no conflicts of interest.