P17.07.A Metronomic temozolomide therapy in heavily pretreated patients with recurrent glioblastoma: a large mono-institutional retrospective study

Abstract

Abstract Background Glioblastoma (GBM) is the most common and aggressive primary brain cancer. Despite advances in surgical and first-line treatment, all pts relapse. The aim of this study is to evaluate the benefit of metronomic Temozolomide (mTMZ) for recurrent GBM. Material and Methods All pts treated at Veneto Institute of Oncology from September 2013 to March 2021 were retrospectively reviewed. Major inclusion criteria were: first-line therapy with Stupp protocol, relapse after first or subsequent line of therapy, treatment with mTMZ schedule (50mg/m2 continuously), hystologically confirmed diagnosis of GBM. RANO criteria and CTCAE v 5.0 were used for response and toxicity assessment. Results 120pts were enrolled. Median follow-up was 15.6ms. Median age was 59ys (range 18-81), ECOG-PS was 0-2 in 107pts (89%) and 3 in 11 (9%). MGMT was methylated and IDH mutated in 66 of 105 (62%) and in 9 of 106 (8%) evaluable pts, respectively. Median number of prior lines of treatment was 2 (range 1-7) and 41% of pts received the therapy beyond the third line. Median time between the last standard maintenance TMZ (sTMZ) cycle and the mTMZ administration was 6ms (range 1-50) and 40% of pts started mTMZ after 3ms from sTMZ. All pts were evaluable for response: 3 (2%) and 48 (40%) showed PR and SD. mOS from the start of mTMZ was 5.4ms (95% CI 4.3-6.4), mPFS was 2.6ms (95% CI 2.3-2.8). At univariate analysis, MGMTmet and MGMTunmet pts had a mOS of 5.6 and 4.4ms (p=0.03); mOS for patients with ECOG-PS > or ≤2 was 2.3 and 6.0ms (p<0.001); number of prior lines of therapies, time between sTMZ and mTMZ and age were not significant. At multivariate analysis, MGMT methylated status (HR=2.3, 95% CI, p=0.004) and ECOG-PS (HR=0.5, 95% CI, p=0.017) remained statistically significant for PFS, while ECOG-PS (HR=0.4, 95% CI, p=0.001) was the only factor significantly associated with OS. The most common grade 3-4 hematologic toxicities were lymphopenia (10%) and thrombocytopenia (3%). Grade 3-4 nonhematologic toxicities were uncommon. Conclusion Rechallenge with mTMZ can be a well tolerated treatment option for recurrent GBM, even in heavily pretreated pts. Pts with MGMTmet and good ECOG-PS might report the major benefit.