Dataset Information

Phase II Study to Evaluate the Efficacy and Safety of Rilotumumab and Bevacizumab in Subjects with Recurrent Malignant Glioma.

ABSTRACT: LESSONS LEARNED:Due to evolving imaging criteria in brain tumors and variation in magnetic resonance imaging evaluation, it is not ideal to use response rate as a primary objective. Future studies involving antiangiogenic agents should use overall survival.Disease-expected toxicities should be considered when defining the clinical significance of an adverse event. For example, vascular thromboembolic events are common in brain tumor patients and should not be attributed to the study drug in the safety analysis. BACKGROUND:Recurrent malignant glioma (rMG) prognosis is poor, with a median patient survival of 3-11 months with bevacizumab (BEV)-containing regimens. BEV in rMG has 6-month progression free survival (PFS-6) of ?40% and an objective response rate of 21.2%. BEV-containing regimens improve PFS-6 to 42.6%-50.3%, indicating that BEV combination therapies may be superior to single agent. Rilotumumab, a hepatocyte growth factor (HGF) antibody, inhibits angiogenesis and expression of angiogenic autocrine factors (e.g., vascular endothelial growth factor [VEGF]) by c-Met inhibition. Combination of rilotumumab with BEV to block vascular invasion and tumor proliferation may synergistically inhibit tumor growth. METHODS:Thirty-six BEV-naïve rMG subjects received rilotumumab (20 mg/kg and BEV (10 mg/kg) every 2 weeks. Endpoints included objective response rate (using Response Assessment in Neuro-Oncology [RANO] criteria), PFS-6, overall survival (OS), and toxicity. RESULTS:Median patient follow-up was 65.0 months. Objective response rate was 27.8% (95% confidence interval [CI]: 15.7%-44.1%). Median OS was 11.2 months (95% CI: 7-17.5). PFS-6 was 41.7% (95% CI: 25.6%-57.0%). Most frequent treatment-related grade ?2 events included weight gain, fatigue, allergic rhinitis, and voice alteration; grade ?3 events included venous thromboembolism (four patients), including one death from pulmonary embolism. CONCLUSION:Rilotumumab with BEV did not significantly improve objective response compared with BEV alone, and toxicity may preclude the use of rilotumumab in combination BEV regimens.

SUBMITTER: Affronti ML

PROVIDER: S-EPMC6156179 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Phase II Study to Evaluate the Efficacy and Safety of Rilotumumab and Bevacizumab in Subjects with Recurrent Malignant Glioma.

Affronti Mary Lou ML Jackman Jennifer Gamboa JG McSherry Frances F Herndon James E JE Massey Elwood C EC Lipp Eric E Desjardins Annick A Friedman Henry S HS Vlahovic Gordana G Vredenburgh James J Peters Katherine B KB

The oncologist 20180417 8

<h4>Lessons learned</h4>Due to evolving imaging criteria in brain tumors and variation in magnetic resonance imaging evaluation, it is not ideal to use response rate as a primary objective. Future studies involving antiangiogenic agents should use overall survival.Disease-expected toxicities should be considered when defining the clinical significance of an adverse event. For example, vascular thromboembolic events are common in brain tumor patients and should not be attributed to the study drug ...[more]

PMID: 29666296

Similar Datasets

Project description:OBJECTIVE: To explore the safety, efficacy, and biomarkers of bevacizumab with gemcitabine and oxaliplatin in women with recurrent platinum-sensitive ovarian carcinoma. METHODS: The patients received bevacizumab (10 mg/kg), gemcitabine (1000 mg/m(2)), and oxaliplatin (65 mg/m(2)) on days 1 and 15 in 28-day cycles. The patients with safely accessible tumor underwent intratumoral fluid pressure (IFP) measurements and positron-emission tomographies immediately and 2 weeks after treatment. Blood biomarkers were evaluated at 5 time points. RESULTS: The trial was closed after enrolling 19 of the 53 projected patient accrual. Thirteen (68.5%) of 19 patients showed a response (1 complete response, 12 partial responses), and 6 patients showed stable disease (31.6%). Median progressive-free survival was 36.9 weeks (258.3 days), and the median overall survival was 112.3 weeks (633 days, not reached). Toxicity was acceptable, and there were no arterial thromboses, serious bleeding, gastrointestinal perforations, or complications from the invasive procedures. Bevacizumab with chemotherapy induced a substantial drop in tumor IFP after treatment. The regimen induced sustained elevation in circulating plasma vascular endothelial growth factor (VEGF), placental growth factor (PlGF), basic fibroblast growth factor (bFGF), soluable vascular endothelial growth factor receptor 2 (sVEGFR2), and circulating progenitor cells. Plasma PlGF, VEGFR2(+) monocytes, and urinary matrix metalloproteinase 2 activity showed differential associations with treatment outcome when evaluated at baseline and after 14 days of treatment. CONCLUSIONS: Despite early termination of the study, the results indicate that the regimen was well tolerated and demonstrated activity in platinum-sensitive ovarian cancer. Biomarker evaluations showed that bevacizumab with chemotherapy significantly changed the levels of several circulating cellular and molecular biomarkers. The increases in plasma PlGF and VEGFR2(+) monocytes showed correlations with outcome. These exploratory data should be further evaluated in future studies of bevacizumab in ovarian cancer.

Dataset Information

Phase II Study to Evaluate the Efficacy and Safety of Rilotumumab and Bevacizumab in Subjects with Recurrent Malignant Glioma.

Publications

Phase II Study to Evaluate the Efficacy and Safety of Rilotumumab and Bevacizumab in Subjects with Recurrent Malignant Glioma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets