2018 Background: Current standard treatment for GBM consists in radiotherapy (RT) plus concomitant and adjuvant (adj) TMZ. Myelosupression is the dose limiting toxicity of TMZ with grade 3 and 4 cytopenia occurring in ~16%. We describe the difference in outcome of newly diagnosed GBM patients treated with TMZ who developed grade 3 and 4 cytopenia. Methods: A 10-year retrospective analysis of newly diagnosed adult GBM patients (pts) treated with first-line TMZ. All pts received concurrent TMZ and RT with or without investigational drug. If the pt did not progress on magnetic resonance imaging (MRI) adj TMZ was given. Cytopenia events during TMZ therapy were graded using the National Cancer Institute Common Toxicity Criteria (v3). Survival distribution was estimated by the Kaplan-Meier method. Results: Of 191 pts, 23% developed grade 3 and 4 cytopenia. 74% pts were ≤ 65 years, 75% had 80-100% karnofsky performance status and 78% had surgical resection at diagnosis. 93% pts received 6 wks of concurrent RT 60 Gy and TMZ 75 mg/m2/d. The median dose of adj TMZ was 150-200 mg/m2/d1-d5 every 28d cycle. The median cycles was 4 (range, 0-24). The median progression free survival (PFS) was 6.7 months (mo). The 6 mo and 12 mo PFS for pts who had grade 3 and 4 cytopenia was 73% (95% confidence interval [CI], 57%-83%) and 33% (95% CI, 20%-47%); while in pts with no grade 3 and 4 cytopenia was 51% (95% CI, 43%-59%) and 24% (95% CI, 17.9%-31.8%). The unadjusted hazard ratio (HR) for death or disease progression of pts with grade 3 and 4 cytopenia, as compared to those without grade 3 and 4 cytopenia, was 0.58 [95% CI, 0.40 to 0.82; p< 0.003]. The HR for death or disease progression was 0.68 (95% CI, 0.47-0.98; p<0.045) among those with a methylated MGMT promoter. The total dose of TMZ was not different between both groups (p=0.284 by Wilcoxon rank sum test). Conclusions: Our study supports that newly diagnosed GBM pts who develop grade 3 and 4 cytopenia during TMZ therapy have improved PFS. Further clinical trials are required to validate grade 3 and 4 cytopenia as a potential biomarker for TMZ efficacy in an attempt to optimize and personalize GBM therapy.

e16601 Background: Bevacizumab, an inhibitor of the vascular endothelial growth factor (VEGF), has been shown to improve progression-free survival (PFS) although current data does not support overall survival (OS) benefit. Studies have been designed in an attempt to find a marker for activity albeit ways to predict response to anti-VEGF therapy are currently lacking. Methods: Retrospective chart review of 454 patients exposed to bevacizumab since 2004 to 2009. The study comprised 157 patients with colon cancer, 127 with glioblastoma, 104 with lung cancer and 66 with breast cancer. Group A represented patients that while treated with bevacizumab developed hypertension or, if already hypertensive, required an increase on their antihypertensive regimen. Group B represented patients that while treated with bevacizumab did not develop hypertension or, if already hypertensive, did not require an increase on their antihypertensive regimen. Results: Median survival (Table 1) is significantly higher in group A (607 days) than group B (355 days), with a log-rank p-value of <0.0001. Median PFS (Table 2) is significantly higher in group A (197 days) than group B (117 days) with a log-rank p-value of <0.0001. Next, multivariate analyses were done for OS and PFS using Cox proportional hazards models. Age group, gender, line of treatment, and single agent versus combined use of bevacizumab were not significant predictors on univariate analyses thus only cancer type was entered into the multivariable model with group. The results for OS (Table 3) indicate that being in group B raises the risk of death by 53.3% when holding type of cancer constant. The results for PFS (Table 4) indicate that females have a 27.3% decreased risk of progression than males when holding group and type of malignancy constant. If a patient is in group A their risk of progression decreases by 32.6% when holding gender and type of malignancy constant. Conclusions: Bevacizumab has proven activity across malignancies nevertheless we have yet to determine which specific patients benefit from its use. Our study shows that hypertension is a clinical surrogate of response to bevacizumab and encourages continuation of anti-VEGF therapy while optimizing anti-hypertensive regimen.