bluuebunny/crossref_metadata_2025_split huggingface dataset:
CTNI-05. NRG ONCOLOGY / RTOG 1119: PHASE II RANDOMIZED STUDY OF WHOLE BRAIN RADIOTHERAPY / STEREOTACTIC RADIOSURGERY WITH CONCURRENT LAPATINIB IN PATIENTS WITH BRAIN METASTASES FROM HER2-POSITIVE BREAST CANCER
Authors: Ah Kim In , Winter Kathryn , Sperduto Paul , De Los Santos Jennifer , Peereboom David , Ogunleye Tomi , Boulter Daniel , Cho Kwan Ho , Shin Kyung Hwan , Zoberi Imran , Choi Serah , Palmer Joshua , Liem Ben , Kim Yong Bae , Anderson Bethany , Thakrar Anupama , Muanza Thierry , Kim Michelle , Choi Doo Ho , White Julia , Mehta Minesh 
Published: December 2020

Abstract
Trastuzumab/pertuzumab improved outcomes for patients (pts) with HER2+ breast cancer. Increased survival coupled with limited blood-brain barrier (BBB) penetration of these agents apparently contributes to increased incidence of brain metastases (BM). Lapatinib (L) crosses the BBB and demonstrates activity against BM. Based upon pre/early clinical data, it’s hypothesized that L + whole brain radiotherapy (WBRT) or Stereotactic Radiosurgery (SRS) would improve intracranial control compared to WBRT/SRS (RT) alone. This randomized phase II trial included HER2+ breast cancer pts with ≥ 1 measurable, unirradiated parenchymal BM. Pts were randomized 1:1 to WBRT (37.5 Gy/3 weeks) or SRS +/- concurrent L (1000 mg dailyx6 weeks), andwere stratified by graded prognostic assessment (GPA), use of non-CNS penetrating anti-HER2 therapies, and previous SRS/resection. The primary endpoint was intracranial complete response (CR) rate 12weeks (wk) after RT. Secondary endpoints included objective response rate (ORR), lesion-specific response rate, CNS progression-free survival, and overall survival. 114 of 143 pts were evaluable for 12-wk CR (52 RT, 62 RT+L). Rate of grade 3 and 4 adverse events were 8% and 0% for RT and 29% and 6% for RT+L. 92% and 90% pts received concurrent and adjuvant L per protocol/acceptable variation. There were no significant differences in 12 or 4wk CR rates (p=0.97 and p=0.77); 5.8% and 0% at 12wk and 3.6% and 1.5% at 4wk for RT and RT+L, respectively. The ORR at 4 wk was 42% and 56% (p=0.059, RECIST), 40% and 58% (p=0.027, WHO) in the RT and RT+L, respectively. Although the addition of lapatinib to WBRT/SRS did not improve the 12wk CR rate, it showed meaningful clinical benefit by demonstrating a trend toward improvement of 4 wk ORR. Results of ongoing central review of MRIs using RECIST1.1, WHO and RANO-BM criteria including secondary endpointswill be reported. Support: NCI grants U10CA180868, U10CA180822, UG1CA189867, and Novartis
CTNI-14. A 3-ARM, PHASE IIA TRIAL OF SAFETY & EFFICACY OF OLINVACIMAB, A MONOCLONAL ANTIBODY TO VEGFR2 IN PATIENTS WITH RECURRENT GLIOBLASTOMA MULTIFORME WITH IMAGING AND PK/PD ASSESSMENTS: FINAL REPORT
Authors: Cher Lawrence , Nowak Anna , Iatropoulos George , Bowyer Samantha , Gan Hui , Long Anne Poh , Bynevelt Michael , Jackson Graeme , Lee Seon Young , Lee Weon Sup , Yoo Jin-San 
Published: December 2020

Abstract
The VEGF pathway remains an important target in GBM given its vascularity and autocrine VEGF signalling. Olinvacimab (TTAC-0001) is a fully humanised VEGFR2 Mab that binds and inhibits the receptor. This report assesses the safety, dosing schedules and efficacy of Olinvacimab in recurrent GBM. We conducted a two-site, 3 arm, open-label study of Olinvacimab in recurrent GBM. Eligible patients were ≥18 years with RANO-measurable lesion, KPS ≥ 80, and had completed chemoradiotherapy without prior bevacizumab therapy. We assessed three arms, 8 mg/kg and 12mg/kg weekly for 3 of every 4 weeks, and 12 mg/kg weekly. Three patients were treated in arms 1 and 2 and 6 in arm 3. Safety assessments were performed prior to dose escalation. The main toxicity was development of grade 1 (67%) and 2 (8%%) cutaneous haemangiomas. Common toxicities seen with other VEGF directed therapies, including hypertension, impaired wound healing, and proteinuria were not seen in this cohort. Efficacy was assessed by MRI using RANO criteria. 6 month PFS was 17%, with disease control in 25%, with steroid dose reduction. The longest response was 15 months. On DCE MRI, there was no significant difference in perfusion parameters between baseline and 1st follow-up MRI comparing those with SD and PD. However, 6 of 12 patients showed decreased Ktrans &gt; 20 % of baseline, consistent with an anti-angiogenic effect of Olinvacimab. Pharmacokinetics showed a decreased clearance rate and increased half-life of Olinvacimab compared to the prior Phase I study. Pharmacodynamic studies showed significantly higher levels of angiogenic markers, particularly VEGF-A in those treated at 12mg/kg vs arm 1. VEGF-A, C and D levels were elevated in patients with SD compared to those with PD. Conclusion: Olinvacimab was well tolerated with a different toxicity profile to other VEGFR directed therapies. There were promising responses in 25% of patients.
CTNI-23. IDH1/2wt ANAPLASTIC GLIOMAS OF THE EORTC RANDOMIZED PHASE III INTERGROUP CATNON TRIAL: OVERALL SURVIVAL RELATED TO TREATMENT, MGMT STATUS AND MOLECULAR FEATURES OF GLIOBLASTOMA
Authors: Tesileanu C Mircea S , French Pim , Erridge Sarah , Vogelbaum Michael , Nowak Anna , Sanson Marc , Brandes Alba , Wick Wolfgang , Clement Paul , Baurain Jean , Mason Warren , Wheeler Helen , Weller Michael , Aldape Kenneth , Wesseling Pieter , Kros Johan M , Golfinopoulos Vassilis , Gorlia Thierry , Baumert Brigitta , van den Bent Martin 
Published: December 2020

Abstract

BACKGROUND
The phase III CATNON trial randomized 751 adult patients with newly diagnosed 1p/19q non-codeleted anaplastic glioma to 59.4 Gy radiotherapy +/- concurrent and/or adjuvant TMZ. Here, we present the molecular analysis of the IDH1/2wt subgroup, and associations between molecular characteristics and patient outcomes.

METHODS
CNV data and MGMT promoter methylation status were assessed from EPIC methylation array data. IDH1/2 and H3F3A mutation status were determined with a glioma tailored next-generation sequencing panel and TERT promoter mutation status using a SNaPshot assay. Overall survival (OS) was measured from date of randomization.

RESULTS
Of 654 assessed tumors, 211 (32%) were IDH1/2wt. An H3F3A mutation was present in 14 tumors (K27M: n=10; G34R: n=4). Of the remaining 197 patients, 154 tumors had molecular features of glioblastoma according to cIMPACT-NOW 3 criteria (‘IDH1/2wt astrocytomas WHO IV’), 39 tumors did not (‘IDH1/2wt astrocytomas WHO III’), and 4 had inconclusive molecular data. IDH1/2wt astrocytomas WHO III patients had significantly better survival than WHO IV patients: median OS of 2.83 yrs vs 1.43 yrs respectively [log-rank test: p&lt; 0.001]. Of the 154 IDH1/2wt astrocytoma WHO IV, 55 (36%) were found MGMT promoter methylated. MGMT promoter methylation was prognostic in IDH1/2wt astrocytomas WHO IV patients, with a median OS of 1.86 yrs for methylated vs 1.34 yrs for unmethylated [HR 1.62, p=0.006]. In the IDH1/2wt astrocytomas WHO IV, no effect of concurrent and/or adjuvant TMZ was observed; the HR for OS after RT with any TMZ vs RT alone was 1.31 [95% CI 0.73–2.36, p=0.4] for MGMT promoter methylated and 0.90 [95% CI 0.55–1.45, p=0.7] for unmethylated glioma patients.

CONCLUSIONS
Our study validated the prognostic value of the cIMPACT-NOW 3 criteria. MGMT promoter methylation is prognostic but not predictive for outcome to TMZ treatment in this cohort of IDH1/2wt anaplastic gliomas with molecular features of glioblastoma.
CTNI-24. A PHASE 2 STUDY OF TRAMETINIB FOR PATIENTS WITH PEDIATRIC GLIOMA WITH ACTIVATION OF THE MAPK/ERK PATHWAY. TRAM-01
Authors: Perreault Sébastien , larouche Valérie , Tabori Uri , Hawkins Cynthia , Lippe Sarah , Ellezam Benjamin , Décarie Jean-Claude , Théoret Yves , Metras Marie-Élaine , Sultan Serge , Cantin Édith , Routhier Marie-Ève , Caru Maxime , Legault Geneviève , Bouffet Eric , Lafay-Cousin Lucie , Hukin Juliette , Erker Craig , Jabado Nada 
Published: December 2020

Abstract

BACKGROUND
Pediatric low-grade gliomas (PLGG) are the most frequent brain tumors in children. It is known that the majority of PLGG have activation of the MAPK/ERK pathway.

METHODS
This multicenter phase II included three progressing/refractory PLGG groups: NF1 patients, KIAA1549-BRAF fusion patients and patients with other activation of the MAPK/ERK pathway (excluding V600E). Primary objective is to evaluate overall response rate after daily oral trametinib administration for 18 cycles each 28 days duration. Secondary objectives include the assessment of progression-free survival, tolerability of trametinib, serum levels of trametinib and evaluation of quality of life during treatment.

RESULTS
As of June 1 2020, 37 patients have been enrolled (NF1: 7 patients, KIAA1549-BRAF fusion: 22, other: 8 (including 5 patients with FGFR1 alterations). Median age is 9.3 years (range 2.3–25.4). Median follow-up is 8.8 months (range 0–19.3). Twenty-eight patients are evaluable. Best response includes: 4 partial response (PR) (14%), 5 minor response (MR) (18%), 18 stable disease (64%), 1 progressive disease (3.5%). Median time to response is 2.8 months (range 2.4–11.3). Median duration of response is 8.0 months (range 0.6–16.8. Progression free survival at 12 months is 83.1% (95% CI 70.5–98.0%) and median progression free survival has not reached. Nine patients (24%) discontinued treatment: 3 for progressive disease, 4 adverse events (3 alanine aminotransferase increase, 1 paronychia), 2 for other reasons.

CONCLUSION
Trametinib is a potentially effective targeted therapy for patients with recurrent/refractory PLGG. Overall treatment is well tolerated. This ongoing trial will continue to gather data on response rate, duration of response and safety of trametinib for PLGG.
CTNI-29. CODEL: PHASE III TRIAL OF RT ALONE, RT PLUS TMZ, OR TMZ ALONE FOR NEWLY-DIAGNOSED, 1p/19q CODELETED ANAPLASTIC OLIGODENDROGLIOMA. ANALYSIS FROM THE INITIAL STUDY DESIGN. (NCCTG N0577, ALLIANCE)
Authors: Jaeckle Kurt , Ballman Karla , van den Bent Martin , Giannini Caterina , Galanis Evanthia , Brown Paul , Jenkins Robert , Cairncross Gregory , Wick Wolfgang , Weller Michael , Aldape Kenneth , Dixon Jesse , Anderson S Keith , Cerhan Jane , Wefel Jeffrey S , Klein Martin , Grossman Stuart , Schiff David , Raizer Jeffrey , Dhermain Frederick , Nordstrom Donald , Flynn Patrick , Vogelbaum Michael 
Published: December 2020

Abstract

BACKGROUND
The original 3-arm CODEL design included a radiotherapy (RT)-alone control arm, an RT plus temozolomide (TMZ) arm, and an exploratory TMZ-alone arm. We report the analysis involving patients treated per the initial design.

METHODS
Adults (18+ years) with newly-diagnosed 1p/19q codeleted WHO grade III oligodendroglioma were randomized to RT (5940 cGy) alone (Arm A); RT with concomitant and adjuvant TMZ (Arm B); or TMZ alone (Arm C). Primary endpoint was OS, Arm A vs. B. Secondary comparisons were performed for OS and PFS, comparing pooled RT arms with the TMZ-alone arm.

RESULTS
36 patients were randomized equally to the three arms. At median follow-up of 7.5 years, 83.3% (10/12) TMZ-alone patients had progressed, versus 37.5% (9/24) patients on the RT arms. PFS was shorter in TMZ-alone patients compared to RT-treated patients (HR=3.12; 95% CI: 1.26, 7.69; p=0.014). Death from disease progression occurred in 3/12 (25%) of TMZ-alone patients and 4/24 (16.7%) of RT-treated patients. OS did not statistically differ between arms, although this comparison was underpowered. After adjustment for IDH status (mutated vs. wildtype) in a Cox regression model, with IDH status and RT treatment status as co-variables (Arm C vs pooled A and B), PFS remained shorter for patients not receiving RT (HR= 3.33; 95% CI: 1.31, 8.45; p=0.011), and OS differences remained non-significant ((HR = 2.78; 95% CI 0.58, 13.22, p=0.20). Grade 3+ adverse events occurred in 25%, 42% and 33% patients (Arms A, B and C, respectively). Neurocognitive assessments, comparing baseline and 3 month timepoints, showed no significant differences between arms.

CONCLUSIONS
TMZ-alone treated patients experienced significantly shorter PFS than patients treated on the pooled RT arms, which remained significant when adjusting for IDH status. CODEL has been redesigned to compare the efficacy and toxicity of RT+PCV versus RT+TMZ. Clinicaltrials.gov Identifier: NCT00887146. Support: U10CA180821, U10CA180882, https://acknowledgments.alliancefound.org.
CTNI-33. DEBIO1347, AN ORAL FGFR INHIBITOR: RESULTS FROM A SINGLE CENTER STUDY IN PEDIATRIC PATIENTS WITH RECURRENT/REFRACTORY FGFR ALTERED GLIOMAS
Authors: Farouk Sait Sameer , Rosenblum Marc , Bale Tejus , Haque Sofia , Gilheeney Stephen , Spatz Krisoula , Prince Daniel , Ibanez Katarzyna , Dunkel Ira , Karajannis Matthias 
Published: December 2020

Abstract

BACKGROUND
Oncogenic driver alterations in fibroblast growth factor receptors (FGFRs) are present in a subset of pediatric gliomas. Debio1347 is an orally available, highly selective FGFR 1–3 inhibitor with a favorable safety profile and encouraging preliminary clinical activity in an adult phase 1 study.

METHODS
We treated five children with progressive/refractory CNS tumors harboring an FGFR gene alteration with Debio1347 on single patient use protocols. Patients were treated using the 20 mg tablet formulation at the adult recommended phase 2 dose (80 mg/1.73 m2 ′ BSA once daily).

RESULTS
All adverse events (AEs) were grade 1–2. Most common treatment-related AEs were hyperphosphatemia, ALT elevation and hypoalbuminemia. Two patients met criteria for partial response and two patients had stable disease. A 13-month-old patient with a spinal cord high-grade glioma harboring two FGFR1 mutations had tumor reduction of 96.3% maintained for 11 months. A 26 month-old patient with a pilomyxoid astrocytoma harboring an FGFR1-TACC1 fusion had a tumor reduction of 74.5% maintained for 9 months. Prolonged disease stabilization and clinically significant improvement in visual function was noted in an eight year-old patient with metastatic suprasellar pilomyxoid astrocytoma harboring two FGFR1 mutations (14 months overall and sustained for 6 months off therapy) and in a 14 year-old patient with posterior fossa glioneuronal tumor harboring an FGFR3-TACC3 fusion (26 months and ongoing).

CONCLUSIONS
FGFR targeted therapy with Debio1347 demonstrated tolerable toxicity and promising anti-tumor efficacy in pediatric patients with recurrent/refractory FGFR altered gliomas. Further studies in this population are warranted.
CTNI-34. INITIAL ANALYSIS OF PHASE-III TRIAL - STANDARD CHEMOTHERAPY VS. CHEMOTHERAPY GUIDED BY A CANCER STEM CELL TEST IN RECURRENT GLIOBLASTOMA (NCT03632135)
Authors: Ranjan Tulika , Chen Ricky , Aregawi Dawit , Chaudhary Rekha , Sengupta Soma , Lu-Emerson Christine , Moulding Hugh , Glass Jon , Schroeder Jason , Jubelirer Steven , Anderson Mark 
Published: December 2020

Abstract

BACKGROUND
ChemoID is a cancer stem cell (CSC) cytotoxicity assay for guiding personalized treatment in the clinical trial NCT03632135 using standard-of-care drugs for improving clinical outcomes. The ChemoID assay is a functional test that determines the response to chemotherapy treatments from a panel of FDA approved drugs or their combinations. The trial aims to determine the clinical utility of the ChemoID assay as a predictor of clinical response in recurrent glioblastoma (GBM).

METHODS
The study has been designed as a parallel group controlled clinical trial where participants with recurrent GBM amenable to surgery or biopsy are randomized at a ratio of 1:1 to either standard-of-care chemotherapy chosen by the physician or ChemoID-guided therapy. Response to therapy is measured by MRI imaging (RANO 1.1). The primary endpoint is median overall survival (OS) and secondary endpoints are OS at 6, 9, and 12 months, median progression-free survival (PFS), PFS at 4, 6, 9, and 12 months, objective tumor response, time to recurrence, and quality of life.

RESULTS
A total of 41 participants (29 males, 12 females) have been accrued to the trial thus far with a median age of 61yo. Data from 38 participants (27 males, 11 females) has reached maturity for analysis. 21 participants have been randomized to the assay-guided arm and 17 to the physician-choice arm. From an initial analysis, we observed that 71% (15/21) of the participants in the ChemoID-guided arm are alive and 29% (6/21) are deceased. We also observed that 41% (7/17) of the participants in the physician-choice arm are alive and 59% (10/17) are deceased. This gives the odds of death for the ChemoID-guided arm to be 72% lower than on the physician-guided arm (OR=0.28; (0.07–1.08); p=0.065).

CONCLUSIONS
Our preliminary results indicate that the ChemoID assay has the potential to improve survival of recurrent GBM patients.
CTNI-38. PAMIPARIB IN COMBINATION WITH RADIATION THERAPY (RT) AND/OR TEMOZOLOMIDE (TMZ) IN PATIENTS WITH NEWLY DIAGNOSED (ND) OR RECURRENT/REFRACTORY (R/R) GLIOBLASTOMA (GBM); PHASE 1B/2 STUDY UPDATE
Authors: Piotrowski Anna , Puduvalli Vinay , Wen Patrick , Colman Howard , Campian Jian , Pearlman Michael , Butowski Nicholas , Cloughesy Timothy , Battiste James , Glass Jon , Schiff David , van den Bent Martin , Walbert Tobias , Ahluwalia Manmeet , Badruddoja Michael , Kalra Amandeep , Pelham Robert , Zhang Kathy , Wood Katie , Weller Michael , Shih Kent 
Published: December 2020

Abstract
Pamiparib, an investigational, oral PARP 1/2 inhibitor, demonstrated preclinical brain penetration and synergistic cytotoxicity with TMZ. We report updated safety and antitumor data for pamiparib plus RT and/or TMZ in ND-GBM or R/R-GBM (SNO 2019, ACTR-39). This dose-escalation/expansion study includes three arms: A, pamiparib (2, 4, or 6 weeks) plus RT (6–7 weeks) in ND-GBM with unmethylated MGMT promoter (unmethylated-GBM); B, pamiparib (6 weeks) plus RT and increasing TMZ doses in Weeks 1 and 5 of RT in unmethylated ND-GBM; and C, pamiparib plus increasing TMZ doses in methylated/unmethylated R/R-GBM. Most patients in Arms A (expansion) and B received maintenance pamiparib plus TMZ after post-RT rest period at Arm C expansion. As of April 10, 2020, enrollment was complete (N=116; A, n=60; B, n=9; C, n=47). Median study follow-up was 11.3 mo (A/B) and 7.1 mo (C). Common grade ≥3 AEs were anemia (10%) in Arm A; decreased neutrophil and white blood cell count (each 22%) in B; anemia, fatigue, and decreased lymphocyte count (each 11%) in C. Brain edema (A) and pneumonia (C) (n=1 each) were fatal treatment-unrelated AEs. In ND-GBM, modified disease control rate (DCR following post-RT rest period) was 69.8% (95% CI, 55.7–81.7) overall, 68.8% (50.0–83.9) in A, and 80.0% (28.4–99.5) in B. Median duration of response was 5.1 mo (overall), 3.8 mo (A), and NE (B). In Arms A/B, median progression-free survival (PFS) and median overall survival (OS) were 4.4 mo and 12.7 mo, respectively; 12-mo OS rate, 54% (95% CI, 40–66). In R/R-GBM (Arm C), confirmed ORR was 9.1% (95% CI, 2.5–21.7); median PFS and OS were 1.9 mo and 7.3 mo, respectively; 6-mo PFS rate, 19% (95% CI, 9–32). These results showed a manageable safety profile for pamiparib +/- RT +/-TMZ; response and survival results support further evaluation of these combinations in GBM.
CTNI-42. FIRST-IN-HUMAN FLUORESCENCE GUIDED SURGERY OF HIGH-GRADE GLIOMAS USING PANITUMUMAB-IRDYE800
Authors: Zhou Quan , van den Berg Nynke , Nishio Naoki , Lu Guolan , Chirita Stefania , Raymundo Roan , Yi Grace , Vogel Hannes , Cayrol Romain , Rosenthal Eben , Li Gordon 
Published: December 2020

Abstract

INTRODUCTION
High-grade gliomas (HGGs) are malignant brain tumors with devastating prognosis. Extent of resection predicts survival in patients, but current neuroimaging approaches lack tumor specificity. The epidermal growth factor receptor (EGFR) is a biomarker heterogeneously expressed in HGGs. We assessed the feasibility of imaging HGGs using a near-infrared fluorescent anti-EGFR antibody.

METHODS
Nine patients with contrast enhancing HGGs on presurgical MRI scan were systemically infused with a flat dose of either 50mg (n = 4) or 100mg (n = 5) panitumumab-IRDye800, 1–5 days before surgery. Near-infrared fluorescence imaging of tumor and histologically normal brain tissues was performed intraoperatively and ex vivo. Fluorescence was measured as mean fluorescence intensity (MFI), and tumor-to-background ratio (TBR) were calculated by comparing MFIs of tumor and histologically uninvolved tissue. Immunohistopathological staining of EGFR was performed on formalin fixed paraffin embedded tissue sections.

RESULTS
Both MFI and TBR were positively correlated to panitumumab-IRDye800 dose per body weight (R2 = 0.59 and 0.07, P &lt; 0.0001 and P = 0.046 respectively). The TBR was higher at a 100 mg dose than at 50 mg (2.1 vs. 1.5). The smallest detectable tumor volume in a closed-field setting was 21 mg with 50 mg of dye and 12 mg with 100 mg. On sections of paraffin embedded tissues, positive EGFR protein expression was observed in 88.9% ± 12.4% of tumor tissues and positively correlated with fluorescence. Sensitivity and specificity of tumor fluorescence for viable tumor detection was calculated and fluorescence was found to be highly sensitive (93%) and specific (81%) for viable tumor tissues while normal brain tissues showed minimal fluorescence. No adverse events related to the imaging probe was observed.

CONCLUSION
This first-in-human study demonstrates the feasibility and safety of antibody based imaging for contrast enhancing high-grade gliomas.
CTNI-43. ANLOTINIB COMBINED WITH STUPP REGIMEN IN TREATING PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA MULTIFORME: A PHASE II PILOT STUDY
Authors: Lai Shuzhen , Chen Yuanyuan 
Published: December 2020

Abstract

PURPOSE
Anlotinib, an orally multi-target tyrosine kinase inhibitor, inhibits tumor angiogenic and proliferative signal pathways. We performed a phase II trial of anlotinib in combination with the STUPP regimen in patients with newly diagnosed glioblastoma multiforme（GBM）to determine whether the combination therapy would safely improve outcomes in this group of patients. An initial pilot study assessed interim safety and tolerability.

METHODS AND MATERIALS
Ten newly diagnosed GBM patients were included in this study. All patients received standard radiation of 60 Gy in 30 fractions starting within 4–6 weeks after surgery with concurrent TMZ (daily, 75 mg/m2) and anlotinib (8mg per day, from day 1 to 14, every 3 weeks). After a 4-week break, adjuvant therapy including 6 cycles of TMZ (150–200 mg/m², from day 1 to 5, every 4 weeks) and 8 cycles of anlotinib (8mg per day, from day 1 to 14, every 3 weeks) was given. For patients completing adjuvant therapy, anlotinib alone (8mg per day, from day 1 to 14, every 3 weeks) was administrated until disease progression.

RESULTS
All patients completed concurrent chemo-radiotherapy without interruption. One patient developed grade 3 weight loss at 56th week and grade 3 presumed radiation-induced cognitive disturbance at 60th week. Fatigue and hypertension were frequently observed during treatment, which potentially be related to the treatment. No severe toxicity was observed in other patients. Up to this writing, none of these patients developed disease progression.

CONCLUSION
Anlotinib combined with the STUPP regimen is a potential choice for newly diagnosed GBM patients. It is well tolerated and the toxicity is manageable. It’s acceptable to continue enrolling of this Phase II study.