BAYPAN study: a double-blind phase III randomized trial comparing gemcitabine plus sorafenib and gemcitabine plus placebo in patients with advanced pancreatic cancer

Gonçalvès, Anthony; Gilabert, Marine; François, Ετιεννε; Dahan, Laétitia; Perrier, H.; Lamy, R.; Ré, Daniel; Largillier, R.; Gasmi, Mohamed; Tchiknavorian, X.; Esterni, Benjamin; Genre, Dominique; Moureau-Zabotto, L.; Giovannini, Marc; Seitz, J.-F.; Delpero, Jean‐Robert; Turrini, Olivıer; Viens, Patrice; Raoul, Jean‐Luc

doi:10.1093/annonc/mds135

Cited by 194 publications

(89 citation statements)

References 27 publications

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“…Figure 1 outlined the selection process in detail. These trials represented three studies with sorafenib, 21,31,32 three with sunitinib, 20,33,34 three with vandetanib [35][36][37] and five with pazopanib. 2,[38][39][40][41] The characteristics of each included trial were presented in Table 2.…”

Section: Resultsmentioning

confidence: 99%

“…Recently, a systematic review and meta-analysis of RCTs with two VEGFR-TKIs (sunitinib and sorafenib) demonstrates a significant increase in the risk of ATEs with these agents, 18 and the anti-vascular endothelial growth factor agent bevacizumab has also been associated with an increase risk of VTEs in previous research. 19 In addition, VEGFR-TKIs associated VTEs have been sporadically reported in severally trials in advanced solid tumors with incidence ranging from 0.3% to 15.4%, 20,21 but the contribution of VEGFR-TKIs to VTEs remains poorly defined due to a limited number of patients included in the trials. The mechanism of angiogenesis induced-VTEs may be directly related to inhibitory effect on VEGF signaling pathway: angiogenesis inhibitors can disrupt the regenerative capacity of endothelial cells (ECs) and cause vascular wall defects, exposing prothrombotic phospholipids on the luminal plasma membrane and the underlying matrix, thus leading to thrombosis.…”

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confidence: 99%

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Risk of venous thromboembolic events associated with VEGFR‐TKIs: A systematic review and meta‐analysis

Min

Shen

et al. 2012

Intl Journal of Cancer

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Vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) have been widely used in advanced cancers. Concerns have arisen regarding the risk of venous thromboembolism with the use of these drugs. Currently, the contribution of VEGFR-TKIs to venous thromboembolism is still unknown. We performed a meta-analysis to determine the incidence and relative risk (RR) of venous thromboembolism events (VTEs) associated with these agents. Eligible studies included phase II and III prospective trials evaluating US Food and Drug Administration approved VEGFR-TKIs (pazopanib, sunitinib, sorafenib and vandetanib), and data on VTEs were available. Overall incidence rates, RR and 95% confidence intervals (CI) were calculated employing fixed-or random-effects models depending on the heterogeneity of included trials. A total of 14 studies (4,430 patients) were selected for this meta-analysis. The incidence of VTEs related to VEGFR-TKIs was 3% (95%CI: 1.7-5.1%), and there was no statistically significant increase in the risk of VTEs for VEGFR-TKIs versus controls in overall population (RR0.912, 95%CI: 0.617-1.348, p 5 0.643). On subgroup analysis, no significant increase in the risk of VTEs was found among different VEGFR-TKIs or tumor types. No evidence of publication bias was observed. The use of VEGFRTKIs does not significantly increase the risk of VTEs, the risk of VTEs in patients with cancer is driven predominantly by tumor types, host factors and concomitant usage of anticancer agents. These results would provide important information for clinicians who use VEGFR-TKIs to treat patients with solid cancer.

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

Risk of venous thromboembolic events associated with VEGFR‐TKIs: A systematic review and meta‐analysis

Min

Shen

et al. 2012

Intl Journal of Cancer

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“…The thick stroma and tumor micro-environment have often been blamed for inadequate drug delivery and the complex genetic signaling for lack of chemotherapy efficacy. Yet noncytotoxic treatments have failed to improve on these modest results with several negative clinical trials, including EGFR, VEGF, BRAF and MMP inhibitors all of which failed to significantly improve overall survival when combined with gemcitabine compared with standard treatment [4][5][6][7]. The only positive outcome from a Phase III trial was with the combination of gemcitabine and the anti-EGFR tyrosine kinase inhibitor erlotinib, the benefits of which were minimal and remains the only nonchemotherapeutic agent to be used for this disease [4].…”

Section: Pancreatic Cancermentioning

confidence: 99%

PAK4 Pathway as a Potential Therapeutic Target in Pancreatic Cancer

2018

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“…However, as this increase was not considered clinically relevant by most oncologists erlotinib has not been broadly adopted as part of standard of care. Other targeted therapies in combination with gemcitabine that have been investigated, including monoclonal antibodies such as bevacizumab and cetuximab or antiangiogenic multikinase inhibitors such as axitinib and sorafenib, have failed to show survival benefit in advanced pancreatic cancer [59][60][61][62][63]. Development of the once-promising hedgehog signaling pathway inhibitor vismodegib (GDC 0449) for the treatment of advanced pancreatic cancer was discontinued recently due to unfavorable results.…”

Section: Targeted Therapiesmentioning

confidence: 99%

Recent Developments and Current Issues in the Treatment of Pancreatic Cancer

Oettle¹

2013

JCT

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Presently, many questions exist about what the optimal regimen comprises for all stages and treatment settings for pancreatic cancer. Since the CONKO-001 trial, adjuvant therapy following resection has become standard of care; however, outcomes are poor, with most patients experiencing disease recurrence, and new therapies have yet to be validated. Furthermore, the value of adjuvant radiotherapy has still not been clearly defined. Targeted treatment in combination with chemotherapy has been mostly disappointing so far in the adjuvant setting but immunotherapy holds potential for improving survival outcomes. Neoadjuvant treatment does not appear to provide much benefit in resectable patients but in the small subgroup of patients with borderline resectable/unresectable locally advanced disease it may increase the possibility of an R0 resection and, consequently, a substantial increase in survival duration. Use of capecitabine-based radiotherapy in patients with unresectable locally advanced disease appears to be more efficacious and better tolerated than gemcitabine-based chemoradiotherapy, with respect to survival outcomes. However, as with adjuvant treatment, the benefit of adding radiotherapy has not yet been definitively demonstrated. In patients with metastatic pancreatic cancer, targeting the stroma with nab-paclitaxel has shown promising results in a phase III trial setting when administered in combination with gemcitabine and, furthermore, this regimen is suitable for a broad range of patients due to its generally good tolerability profile. Because of its high toxicity, FOLFIRINOX is more suitable for younger patients with an excellent performance status who can withstand aggressive treatment and in patients with a worse performance status, gemcitabine monotherapy is considered to be a more appropriate treatment. Alternatively, gemcitabine in combination with erlotinib, the only targeted compound that has resulted in significant albeit small improvements in survival in patients with advanced disease, could be selected. However, the benefit-risk profile of this regimen is only favorable in a strictly defined, small patient subgroup who develop a treatment-related rash. Finally, with the elucidation of prognostic and predictive markers, treatment is expected to become ever more individualized, leading to improved efficacy outcomes and less unnecessary toxicity.

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BAYPAN study: a double-blind phase III randomized trial comparing gemcitabine plus sorafenib and gemcitabine plus placebo in patients with advanced pancreatic cancer

Cited by 194 publications

References 27 publications

Risk of venous thromboembolic events associated with VEGFR‐TKIs: A systematic review and meta‐analysis

Risk of venous thromboembolic events associated with VEGFR‐TKIs: A systematic review and meta‐analysis

PAK4 Pathway as a Potential Therapeutic Target in Pancreatic Cancer

Recent Developments and Current Issues in the Treatment of Pancreatic Cancer

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