A meta-analysis of antiangiogenic therapy for glioblastoma (GBM).
Central Nervous System Tumors
Central Nervous System Tumors
2014 ASCO Annual Meeting
J Clin Oncol 32:5s, 2014 (suppl; abstr 2047)
2014 ASCO Annual Meeting!
Session: Central Nervous System Tumors
Type: General Poster Session
Time: Saturday May 31, 1:15 PM to 5:00 PM
Location: S Hall A2
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Author(s): Mustafa Khasraw, Malaka Ameratunga, Andrew B. Lassman, David M. Ashley, Helen Wheeler, Nick Pavlakis; Andrew Love Cancer Centre, Geelong, Australia; Barwon Health, Geelong, Australia; Columbia University Medical Center, New York, NY; Deakin University, Geelong, Australia; Royal North Shore Hospital, Sydney, Australia; Department of Medical Oncology, Royal North Shore Hospital, The University of Sydney, Sydney, Australia
Background: Overall Survival (OS) and Progression Free Survival (PFS) results of randomized controlled trials (RCTs) are available of anti-angiogenic therapy (AAT) in GBM, especially Bevacizumab (Bev). Methods: Searches were conducted to identify published and unpublished RCTs starting in 2000 including The Cochrane Central Register of Controlled Trials (CENTRAL); MEDLINE and EMBASE. Proceedings of relevant oncology conferences from 2000 to 1/ 2014, were also searched. RCTs with random allocation of the use of AATs to treat GBM were included. Authors screened search results and reviewed abstracts of potentially relevant articles before retrieving the full text of eligible articles. Results: Seven eligible RCTs were identified including 3187 patients. There was significant heterogeneity in studies especially in response assessment criteria. Six studies were only available in abstract form. Trials included in this analysis did not show improvement in OS with a pooled hazard ratio (HR) of 0.95 (95% CI 0.87 to 1.04; P = 0.27). They did however demonstrate improvement in PFS with improvement in the HR for PFS at 0.74 (95% CI 0.68 to 081; P= 0.00001). The HRs of the studies containing Bev as the AAT were generally more likely to report favorable results than other AAT, the pooled HR for PFS for Bev studies (n = 1712 patients) was significant at 0.57 (95% CI 0.4 to 0.82; P = 0.002). In the adjuvant setting with 5 RCTs including 2441 patients (AVAGLIO, RTOG 0825, GLARIUS with Bev; CENTRIC and CORE with cilengitide), the HR for OS was 0.90 (P = 0.19). Pooled analysis for PFS in the adjuvant setting (4 studies, n= 2441) showed significant HR at 0.69 (95% CI 0.56, 0.85; P= 0.0006). In the recurrent setting pooling of 2 RCTs (n=576) namely the phase 3 with cediranib (REGAL) and the phase 2 study with Bev (BELOB) showed HR for OS was 1.02 (P = 93). The BELOB study did not report PFS i.e., there is no RCT data to assess PFS with Bev in recurrent GBM. Conclusions: Bev appears to prolong PFS in newly diagnosed GBM. Available data does not demonstrate a survival benefit in newly diagnosed patients. In the recurrent setting, there is no adequately powered RCT to address if there is a PFS or survival benefit with Bev. A more detailed analysis is prepared as a Cochrane systematic review.
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