Tomohiro Funakoshi1, Asma Latif2, Matthew D Galsky3. 1. Department of Medicine, Beth Israel Medical Center, University Hospital and Manhattan Campus for the Albert Einstein College of Medicine, New York, United States. Electronic address: tfunakoshi@chpnet.org. 2. Division of Hematology/Oncology, Tisch Cancer Institute, Mount Sinai School of Medicine, New York, United States. Electronic address: asma.latif@mountsinai.org. 3. Division of Hematology/Oncology, Tisch Cancer Institute, Mount Sinai School of Medicine, New York, United States. Electronic address: matthew.galsky@mssm.edu.
Abstract
BACKGROUND: The approach of combining cytotoxic chemotherapy with oral small molecule tyrosine kinase inhibitors (TKIs) has been explored in a large number of randomized trials, in a variety of tumor. We performed a systematic review and meta-analysis to evaluate the safety and efficacy of this therapeutic approach. PATIENTS AND METHODS: PubMed and the ASCO databases were searched up to March 2013. We included randomized trials in which the FDA approved vascular endothelial growth factor receptor (VEGFR) or epidermal growth factor receptor-family (EGFR)-targeted TKI in combination with chemotherapy was compared with chemotherapy alone in patients with any type of solid cancer. The endpoints included safety [fatal adverse events (FAEs), treatment discontinuation, any severe (grade 3 or 4) adverse events (AEs), and individual severe AEs] and efficacy [progression-free survival (PFS), and overall survival (OS)]. The pooled relative risk (RR) or hazard ratio (HR) were calculated. RESULTS: A total of 16,011 patients from 43 trials were included. Compared with chemotherapy alone, the addition of a TKI significantly increased the risk of FAEs (RR, 1.63; 95% CI, 1.32-2.01), treatment discontinuation (RR, 1.80; 95% CI, 1.58-2.06), and any severe AE (RR, 1.25; 95% CI, 1.16-1.36). The addition of a TKI was associated with a significant improvement in PFS (HR, 0.82; 95% CI, 0.76-0.89), but not OS (HR, 0.99; 95% CI, 0.95-1.03). CONCLUSIONS: It is important for physicians to weigh the risk of toxicity versus the modest PFS benefit associated with chemotherapy plus TKI in patients with solid cancers.
BACKGROUND: The approach of combining cytotoxic chemotherapy with oral small molecule tyrosine kinase inhibitors (TKIs) has been explored in a large number of randomized trials, in a variety of tumor. We performed a systematic review and meta-analysis to evaluate the safety and efficacy of this therapeutic approach. PATIENTS AND METHODS: PubMed and the ASCO databases were searched up to March 2013. We included randomized trials in which the FDA approved vascular endothelial growth factor receptor (VEGFR) or epidermal growth factor receptor-family (EGFR)-targeted TKI in combination with chemotherapy was compared with chemotherapy alone in patients with any type of solid cancer. The endpoints included safety [fatal adverse events (FAEs), treatment discontinuation, any severe (grade 3 or 4) adverse events (AEs), and individual severe AEs] and efficacy [progression-free survival (PFS), and overall survival (OS)]. The pooled relative risk (RR) or hazard ratio (HR) were calculated. RESULTS: A total of 16,011 patients from 43 trials were included. Compared with chemotherapy alone, the addition of a TKI significantly increased the risk of FAEs (RR, 1.63; 95% CI, 1.32-2.01), treatment discontinuation (RR, 1.80; 95% CI, 1.58-2.06), and any severe AE (RR, 1.25; 95% CI, 1.16-1.36). The addition of a TKI was associated with a significant improvement in PFS (HR, 0.82; 95% CI, 0.76-0.89), but not OS (HR, 0.99; 95% CI, 0.95-1.03). CONCLUSIONS: It is important for physicians to weigh the risk of toxicity versus the modest PFS benefit associated with chemotherapy plus TKI in patients with solid cancers.
Authors: Matthew D Galsky; Marshall Posner; Randall F Holcombe; Karen M Lee; Krzysztof Misiukiewicz; Che-Kai Tsao; James Godbold; Rothschild Soto; Kiev Gimpel-Tetra; Nancy Lowe; William K Oh Journal: Cancer Chemother Pharmacol Date: 2014-07-15 Impact factor: 3.333
Authors: Antonella Borgatti; Ann Fieberg; Amber L Winter; Kathleen Stuebner; Elizabeth Taras; Deborah Todhunter; Alison Masyr; Aaron Rendhal; Daniel A Vallera; Joseph S Koopmeiners; Jaime F Modiano Journal: Vet Comp Oncol Date: 2020-04-02 Impact factor: 2.613
Authors: Antonella Borgatti; Joseph S Koopmeiners; Aaron L Sarver; Amber L Winter; Kathleen Stuebner; Deborah Todhunter; Anthony E Rizzardi; Jonathan C Henriksen; Stephen Schmechel; Colleen L Forster; Jong-Hyuk Kim; Jerry Froelich; Jillian Walz; Michael S Henson; Matthew Breen; Kerstin Lindblad-Toh; Felix Oh; Kristy Pilbeam; Jaime F Modiano; Daniel A Vallera Journal: Mol Cancer Ther Date: 2017-02-13 Impact factor: 6.009