374P Temozolamide (TMZ) rechallenge at standard or metronomic dose versus other treatments in patients (pts) with high grade glioma with TMZ free-interval (TFI) longer than 3 months (mo)
Annals of Oncology(2020)
摘要
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. 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. 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). 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.
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关键词
high grade glioma,tmz,metronomic dose,other treatments,free-interval
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