Avash Das1, Somnath Mahapatra2, Dhrubajyoti Bandyopadhyay3, Santanu Samanta4, Sandipan Chakraborty5, Lisa Liang Philpotts6, Eiman Jahangir7, Bhaskar Roy8. 1. Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: Avash.Das@UTSouthwestern.edu. 2. Department of Pathology, University College of Medical Sciences, New Delhi, India. 3. Division of Internal Medicine, St. Luke Roosevelt Medical Center, Mount Sinai, NY, USA. 4. Department of Radiation Oncology, University of Maryland, MD, Baltimore, USA. 5. Department of Internal Medicine, Interfaith Medical Center, NY, USA. 6. Treadwell Library, Massachusetts General Hospital, Boston, MA, USA. 7. Divisions of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. 8. Department of Neurology, Division of Neuromuscular Medicine, Yale School of Medicine, New Haven, CT, USA. Electronic address: bhaskar.roy@yale.edu.
Abstract
BACKGROUND: Targeted therapies like vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) are the first-choice treatment in several types of cancers. We aim to determine the comparative risk of bleeding events associated with the VEGFR-TKIs through a network meta-analysis. METHODS: Published data search up to November 2018 reporting bleeding in cancer patients treated with VEGFR-TKIs was performed. The primary outcome was presence of hemorrhagic events at the end of the trial. Bleeding as a side-effect profile was examined for eleven VEGFR-TKIs (Apatinib, Brivanib, Cabozantinib, Lenvatinib, Motesanib, Nintedanib, Pazopanib, Regorafenib, Sorafenib, Sunitinib and Vandetanib). Network meta-analysis based on random effects model estimating Odds Ratio (OR) with 95 % confidence interval (CI), compared the risk of bleeding events among the VEGFR-TKIs with respect to placebo control conditions. RESULTS: Fifty Randomized Clinical Trials (RCTs) including 16,753 cancer patients were included in this analysis. Twenty studies compared VEGFR-TKIs with placebo, the remaining studies compared VEGFR-TKIs with the standard chemotherapeutic regimen. VEGFR-TKIs were associated with increased incidence of all-grade hemorrhagic events in comparison to control (standard chemotherapy and/or placebo) (OR = 1.79; 95 % CI 1.50-2.13, p-value <0.0001) and placebo (OR = 1.50; 95 % CI 1.16-1.93, p-value = 0.1). However, there was no difference in high-grade bleeding in patients treated with VEGFR-TKI in comparison to control (OR = 1.22; 95 % CI 0.87-1.71, p-value 0.74) or placebo alone (OR = 1.05; 95 % CI 0.65-1.70, p-value 0.73). Among individual VEGFR-TKIs, Sunitinib (OR = 3.31, 95 % CI 2.34-4.69) and Regorafenib (OR = 2.92, 95 % CI 1.50-5.71) were associated with higher risk of hemorrhagic events in comparison to placebo. CONCLUSION: VEGR-TKIs, particularly Sunitinib and Regorafenib appear to be associated with increased risk of bleeding incidence. TRIAL REGISTRATION NUMBER: PROSPERO CRD42017056406.
BACKGROUND: Targeted therapies like vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) are the first-choice treatment in several types of cancers. We aim to determine the comparative risk of bleeding events associated with the VEGFR-TKIs through a network meta-analysis. METHODS: Published data search up to November 2018 reporting bleeding in cancerpatients treated with VEGFR-TKIs was performed. The primary outcome was presence of hemorrhagic events at the end of the trial. Bleeding as a side-effect profile was examined for eleven VEGFR-TKIs (Apatinib, Brivanib, Cabozantinib, Lenvatinib, Motesanib, Nintedanib, Pazopanib, Regorafenib, Sorafenib, Sunitinib and Vandetanib). Network meta-analysis based on random effects model estimating Odds Ratio (OR) with 95 % confidence interval (CI), compared the risk of bleeding events among the VEGFR-TKIs with respect to placebo control conditions. RESULTS: Fifty Randomized Clinical Trials (RCTs) including 16,753 cancerpatients were included in this analysis. Twenty studies compared VEGFR-TKIs with placebo, the remaining studies compared VEGFR-TKIs with the standard chemotherapeutic regimen. VEGFR-TKIs were associated with increased incidence of all-grade hemorrhagic events in comparison to control (standard chemotherapy and/or placebo) (OR = 1.79; 95 % CI 1.50-2.13, p-value <0.0001) and placebo (OR = 1.50; 95 % CI 1.16-1.93, p-value = 0.1). However, there was no difference in high-grade bleeding in patients treated with VEGFR-TKI in comparison to control (OR = 1.22; 95 % CI 0.87-1.71, p-value 0.74) or placebo alone (OR = 1.05; 95 % CI 0.65-1.70, p-value 0.73). Among individual VEGFR-TKIs, Sunitinib (OR = 3.31, 95 % CI 2.34-4.69) and Regorafenib (OR = 2.92, 95 % CI 1.50-5.71) were associated with higher risk of hemorrhagic events in comparison to placebo. CONCLUSION: VEGR-TKIs, particularly Sunitinib and Regorafenib appear to be associated with increased risk of bleeding incidence. TRIAL REGISTRATION NUMBER: PROSPERO CRD42017056406.
Authors: Avash Das; Subhajit Dasgupta; Yan Gong; Urvi A Shah; Michael G Fradley; Richard K Cheng; Bhaskar Roy; Avirup Guha Journal: Hematol Oncol Date: 2021-12-30 Impact factor: 4.850
Authors: Alexander Gudkov; Valery Shirokorad; Kirill Kashintsev; Dmitriy Sokov; Daniil Nikitin; Andrey Anisenko; Nicolas Borisov; Marina Sekacheva; Nurshat Gaifullin; Andrew Garazha; Maria Suntsova; Elena Koroleva; Anton Buzdin; Maksim Sorokin Journal: Front Mol Biosci Date: 2022-03-14