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2028 Background: Clinical outcomes in patients with recurrent high-grade glioma (HGG) remain poor. Cancer stem cells (CSCs) have been implicated in metastasis, treatment resistance and recurrence of HHGs. We have shown in several clinical studies that anti-CSC-directed therapy selected by ChemoID assay provides benefits in many cancer types; however, this is the first report of a randomized clinical trial evaluating whether CSC-targeted cytotoxic agents selected by ChemoID assay-guided therapy improves survival in patients with recurrent HGG. Methods: In this parallel-group, randomized, phase-3 clinical trial, patients at 13 clinical sites in the USA with grade-III/IV recurrent glioma (2016 WHO guidelines) were randomized 1:1 to either ChemoID assay-guided therapy or physician-choice therapy, and then treated and followed until unacceptable toxic effects, hospice, or death. The primary endpoint was overall survival (OS). Results: Combined median follow-up was 9 months. Median OS (mOS) was 12.5 months (95% CI, 10.2-14.7) in the ChemoID assay-guided group vs 9 months (95% CI, 4.2-13.8) in the physician-choice group (log-rank P =.010). Risk of death was significantly lower in the ChemoID assay group (HR = 0.44; 95% CI, 0.24-0.81; P =.008). Median progression free survival (PFS) was 10.1 vs 3.5 months (95% CI, 4.8-15.4 vs 1.9-5.1) (HR, 0.25; 95% CI, 0.14-0.44; P

2540 Background: Glioblastoma (GBM) in elderly patients differ molecularly as compared to younger patients, and may have increased angiogenic activity. Bevacizumab (BV) is an anti-angiogenic monoclonal antibody against vascular endothelial growth factor. We conducted a clinical trial to evaluate the efficacy and safety of BV and temozolomide (TMZ) for elderly patients with a new diagnosis of GBM, while deferring radiotherapy. Methods: This is a phase II, single-arm, multicenter, open label trial. Eligible patients have a tissue diagnosis of GBM with no treatment other than surgery, age ≥ 70, KPS ≥ 60, and adequate organ function. TMZ was initiated within 2 weeks of surgery and BV was initiated within 4 weeks thereafter. TMZ was administered at 150-200 mg/m2/day for 5 days every 4 weeks and BV at 10mg/kg every 2 weeks. A historical control group of 42 patients with similar criteria who received concurrent TMZ and RT followed by adjuvant TMZ, was derived for comparison from an institutional patient database. The primary endpoint is overall survival (OS) and secondary endpoints are progression-free-survival and safety. Results: 50 patients were enrolled from June 2010 to January 2016. Median age is 75 (range 70-87), and median KPS is 80 (range 60-100). 17 patients had a biopsy only, 26 patients have MGMT promoter methylation, and all patients are IDH wildtype. The study and control group are well matched in terms of age and molecular markers, however, the study patients had worse initial KPS and higher baseline tumor volume. At time of analysis, all but 2 patients were deceased. The median OS was 12.6 months for study patients (95% CI, 10.9-15.9 months) and 16.3 months for control patients (95% CI, 12.9-22.4 months). In a multivariate Cox analysis, baseline tumor volume (HR = 2.6, p = 0.0001) and MGMT promoter methylation (HR = 0.49, p = 0.004) were significant prognostic markers. Treatment type did not have a significant impact on OS (HR = 1.5, p = 0.14). Treatment-related serious adverse events included: pulmonary embolism (5), cerebral hemorrhage (3), pneumonia (1), intestinal perforation (1), deep venous thrombosis (6), hypertension (2), atrial fibrillation (1), congestive heart failure (1), cardio-respiratory arrest (1), lymphopenia (2), thrombocytopenia (8), and neutropenia (5). Conclusions: The results of this study suggest for patients with newly diagnosed GBM age ≥70 and KPS ≥60, treatment with BV and TMZ is equivalent to standard chemoradiotherapy, and has tolerable side effects. Complete endpoint analysis will be presented with the poster. Clinical trial information: NCT01149850 .

2052 Background: Bev was FDA approved for recurrent GBM in 2009. However, the survival benefit from Bev in GBM remains to be demonstrated. Methods: We retrospectively identified 168 primary GBM patients diagnosed between 2001-2015 at UCLA and Kaiser Permanente LA, who received upfront radio-chemotherapy, followed with Bev and/or Lomustine (CCNU) at 1st recurrence. We measured tumor size at 1st recurrent treatment initiation, using bi-dimensional (2D) and volumetric (3D) techniques. We analyzed overall survival (OS) from 1st recurrence by Kaplan-Meier analysis. Results: Three groups of patients diagnosed from 2009-2015 were identified: patients treated with Bev alone (n = 49), CCNU alone (n = 36), and concurrent Bev/CCNU (n = 53). Patients were statistically different in performance status at 1st recurrence and tumor size; the CCNU alone group had smaller tumor sizes at diagnosis compared to the Bev groups. The CCNU group showed substantially greater survival (median OS (mOS) = 14.1 mo) compared to the Bev and Bev/CCNU groups (mOS = 6.9 and 7.1 mo, respectively), which may be explained by the imbalance in tumor sizes among the groups, and high rate of crossover (69%) to Bev in subsequent recurrences. To minimize selection bias, we identified another control group (n = 30) diagnosed from 2001-2004 who received CCNU only (CCNU 01-04). These patients had tumor size and KPS more comparable to both Bev groups, and a low rate of crossover (7%). OS for CCNU 01-04 (mOS = 5.7 mo) was similar to the Bev groups. Across all patients, we observed poor OS associated with larger 2D size vs. those with small tumors (mOS = 6.7 vs. 8.8 mo; p = 0.003). In separate stratification of each treatment group by tumor size, this association was retained in the CCNU 01-04 group (mOS = 4.0 vs. 8.4 mo, p < 0.001), but not in either Bev (mOS = 6.7 vs. 7.3 mo) or BEV/CCNU (mOS = 7.0 vs. 8.8 mo). Analysis of effect of tumor size by 3D measurement yielded similar results. Conclusions: Bev appears to reduce the negative impact of large tumor size on GBM patient survival from 1st recurrence. 2D and 3D measurements were correlated, suggesting the adequacy of use of conventional tumor bi-dimensional measurement to predict benefit of Bev in patients based on tumor size.

2012 Background: Randomized clinical trials in newly diagnosed, elderly GBM patients have shown that treatment with temozolomide chemotherapy is at least equivalent to treatment with radiotherapy. Glioblastoma in elderly patients may also have high angiogenic activities. Bevacizumab is an antiangiogenic agent, a humanized monoclonal antibody directed against the vascular endothelial growth factor. We conduct a clinical trial of temozolomide and bevacizumab to evaluate the safety and efficacy of this combination in the treatment of elderly patients with newly diagnosed GBM, good performance status, and willing to forgo upfront treatment with radiation therapy. Methods: This is a phase II trial of newly diagnosed GBM patients age ≥70 with no prior treatments other than surgery and Karnofsky Performance Status (KPS) ≥60. Patients receive treatments 4-6 weeks after surgery with bevacizumab (10mg/kg every 2 weeks) and temozolomide (150-200 mg/m2 for 5 days out of 28 days, up to 12 cycles) until tumor progression. Primary outcome measures are overall survival and safety evaluations. Results: From June 2010 to January 2016, 50 GBM patients enrolled in this study. To date, all patients have tumor progression and 3 are still alive. The median age is 75 (range 70 - 87), and median KPS is 80 (range 60-100). 15 patients have a gross total resection. 26 out of 49 patients with tissues available for evaluation have methylation of the MGMT promoter, and no patient has IDH-1 mutation. Median overall survival is 12.3 months (14.8 months for those with methylation of MGMT, 10.0 months for unmethylated MGMT). Serious adverse events related to treatments include wound healing problems (2), CNS hemorrhage (3), pulmonary embolism (4), and bowel perforation (1). Serious hematological adverse events include thrombocytopenia (3) and neutropenia (5). Conclusions: For patients with newly diagnosed GBM age ≥70, KPS ≥60, treatment with temozolomide and bevacizumab may show promising survival benefits and have tolerable side effects. More detailed safety and efficacy analysis will be presented. Clinical trial information: NCT01149850.

2003 Background: The standard of care for patients with newly-diagnosed glioblastoma (GBM) consists of postoperative radiotherapy and temozolomide (TMZ). O6-methylguanine-DNA methyltransferase (MGM...

2059 Background: Poor postoperative neurologic function due to mass effect and steroid-refractory perilesional edema often limits the ability of patients with glioblastoma multiforme (GBM) to toler...

2060 Background: Ependymoma is a rare type of glioma, representing less than 5% of brain tumors in adults. Radiotherapy (RT) is commonly administered, but there is no standard chemotherapy. At recurrence ependymoma is notoriously refractory to therapy and the prognosis is poor. In recurrent glioblastoma, encouraging responses with bevacizumab have been observed. Therefore, we treated patients with recurrent ependymoma and anaplastic ependymoma with bevacizumab containing chemotherapy regimens. Methods: We retrospectively identified adults treated for recurrent ependymoma and anaplastic ependymoma with bevacizumab containing chemotherapy regimens. We determined radiographic response (Macdonald criteria) and estimated median time to progression (TTP) and overall survival (OS) by the Kaplan-Meier method. Results: There were six patients, four women and two men, with a median age of 29 years (range, 20–65). Prior treatment included RT in all and temozolomide in four. Bevacizumab (5–10 mg/kg) every other week was combined with cytotoxic agents: irinotecan (3), carboplatin (2), or temozolomide (1). Five patients achieved a partial response (83%); in one patient the disease was stable. Median TTP and OS were 6.5 (95% CI: 2.7–10.2) and 9.4 (95% CI: 6.3–12.6) months, respectively, with a median follow up of 18.7 months for the two surviving patients. One additional patient is initiating bevacizumab monotherapy (not included in this analysis). Conclusions: Bevacizuamb has efficacy in the treatment of recurrent ependymoma. Prospective study is warranted. [Table: see text]

2000 Background: Bevacizumab (BV) is a humanized monoclonal antibody directed against the vascular endothelial growth factor (VEGF). Based on the promising activity of BV in the treatment of recurrent glioblastoma, we are conducting a phase II trial to determine whether up-front treatment of newly diagnosed GBM with BV may be more advantageous than withholding BV until recurrence. In this trial, we evaluate the safety and efficacy of BV combined with standard of care radiation (RT) and temozolomide (TMZ) and radiation (RT) for newly-diagnosed GBM. Methods: This is a phase II trial with a 10-patient pilot and 60-patient expansion phases. Newly-diagnosed GBM patients with no prior treatments are eligible. Primary outcome measure is overall survival; the secondary outcome measure is TTP and 12-month survival. Therapy began between 3–5 weeks of surgery with BV (10 mg/kg every 2 weeks), TMZ (75 mg/m2 daily), and external beam RT (30 x 200 Gy) on the same day. After completion of radiation, patients are then placed on a maintenance phase of BV (10mg/kg every 2 weeks) and TMZ (150–200 mg/m2 5 out of every 28 days) until progression or 24 months in which patients are then maintained on BV only. Results: 70 of 70 projected GBM patients have been enrolled between August 2006 and November 2008 at UCLA and Kaiser Permanente (KP) (Northern and Southern California). All patients had resections to ensure that frozen tissue (>200mg) was collected. The median age was 57.4 years (range 31–75). MGMT methylation analysis has been performed on 52/70 patients with ∼40% showing methylation. Severe adverse events to date have included ischemic stroke, pulmonary embolus, wound breakdown, GI bleeding/perforation, and renal dysfunction. Isolated cases of retinal detachment and optic neuropathy have also been observed. As of now, 35/70 patients are off study (26 due to progression and 9 due to SAE). Preliminary TTP by Kaplan-Meier analysis is promising compared to that of a UCLA/KP control group of patients that received the conventional RT/TMZ regimen. Conclusions: Addition of BV to the standard regimen of TMZ and RT for newly-diagnosed GBM is well-tolerated and shows promising efficacy. More detailed analysis of safety and efficacy will presented. [Table: see text]