TY - JOUR
T1 - A Systematic Review and Network Meta-Analysis of Regorafenib and TAS-102 in Refractory Metastatic Colorectal Cancer
AU - Sonbol, Mohamad Bassam
AU - Benkhadra, Raed
AU - Wang, Zhen
AU - Firwana, Belal
AU - Walden, Daniel J.
AU - Mody, Kabir
AU - Hubbard, Joleen M.
AU - Murad, M. Hassan
AU - Ahn, Daniel H.
AU - Bekaii-Saab, Tanios
N1 - Publisher Copyright:
© AlphaMed Press 2019
PY - 2019/9/1
Y1 - 2019/9/1
N2 - Background: Regorafenib at different dosing strategies and TAS-102 are treatment options for refractory metastatic colorectal cancer (mCRC). We aimed to evaluate the comparative effectiveness evidence supporting these different strategies. Materials and Methods: We searched different databases for randomized controlled trials evaluating TAS-102 or regorafenib in patients with refractory mCRC who failed prior oxaliplatin, irinotecan, and fluoropyrimidine. Outcomes of interest included overall survival (OS) and progression-free survival (PFS). The overall effect was pooled using the DerSimonian random effects model. We conducted network meta-analysis based on White's multivariate meta-regression to pool evidence from direct and indirect comparisons. Results: Six trials at low risk of bias (2,445 patients) were included. Direct comparisons showed that Rego 160 and TAS-102 as monotherapy were superior to best-supportive care (BSC) in terms of PFS (Rego 160: hazard ratio [HR], 0.4; 95% confidence ratio [CI], 0.26–0.63; TAS-102: HR, 0.46 CI, 0.40–0.52) and OS (Rego 160: HR, 0.67; CI, 0.48–0.93; TAS-102: HR, 0.67; CI, 0.57–0.80). Network analysis showed no statistically difference in PFS or OS between Rego 160 and TAS-102. Rego 80+ was superior to BSC in terms of OS (HR, 0.44; CI, 0.23–0.84) and PFS (HR, 0.37; CI, 0.21–0.66). Rego 80+ was associated with statistically nonsignificant improvement in OS and PFS compared with TAS-102 and Rego 160. Conclusion: Regorafenib 160 and TAS-102 appear to have similar efficacy. Rego 80+ is shown to be superior to BSC. A trend for improved OS was observed with Rego 80+ versus Rego 160 or TAS 102. Implications for Practice: Regorafenib at a dose of 160 mg and TAS-102 appear to have similar efficacy in patients with refractory metastatic colorectal cancer. Regorafenib with a dose escalation strategy is superior to best-supportive care. Given its tolerability and the observed trend in survival benefit compared with regorafenib 160, dose escalation strategy of regorafenib (80+) may be the preferred option in this setting.
AB - Background: Regorafenib at different dosing strategies and TAS-102 are treatment options for refractory metastatic colorectal cancer (mCRC). We aimed to evaluate the comparative effectiveness evidence supporting these different strategies. Materials and Methods: We searched different databases for randomized controlled trials evaluating TAS-102 or regorafenib in patients with refractory mCRC who failed prior oxaliplatin, irinotecan, and fluoropyrimidine. Outcomes of interest included overall survival (OS) and progression-free survival (PFS). The overall effect was pooled using the DerSimonian random effects model. We conducted network meta-analysis based on White's multivariate meta-regression to pool evidence from direct and indirect comparisons. Results: Six trials at low risk of bias (2,445 patients) were included. Direct comparisons showed that Rego 160 and TAS-102 as monotherapy were superior to best-supportive care (BSC) in terms of PFS (Rego 160: hazard ratio [HR], 0.4; 95% confidence ratio [CI], 0.26–0.63; TAS-102: HR, 0.46 CI, 0.40–0.52) and OS (Rego 160: HR, 0.67; CI, 0.48–0.93; TAS-102: HR, 0.67; CI, 0.57–0.80). Network analysis showed no statistically difference in PFS or OS between Rego 160 and TAS-102. Rego 80+ was superior to BSC in terms of OS (HR, 0.44; CI, 0.23–0.84) and PFS (HR, 0.37; CI, 0.21–0.66). Rego 80+ was associated with statistically nonsignificant improvement in OS and PFS compared with TAS-102 and Rego 160. Conclusion: Regorafenib 160 and TAS-102 appear to have similar efficacy. Rego 80+ is shown to be superior to BSC. A trend for improved OS was observed with Rego 80+ versus Rego 160 or TAS 102. Implications for Practice: Regorafenib at a dose of 160 mg and TAS-102 appear to have similar efficacy in patients with refractory metastatic colorectal cancer. Regorafenib with a dose escalation strategy is superior to best-supportive care. Given its tolerability and the observed trend in survival benefit compared with regorafenib 160, dose escalation strategy of regorafenib (80+) may be the preferred option in this setting.
KW - Refractory metastatic colorectal cancer
KW - Regorafenib
KW - TAS-102
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UR - http://www.scopus.com/inward/citedby.url?scp=85067407602&partnerID=8YFLogxK
U2 - 10.1634/theoncologist.2019-0189
DO - 10.1634/theoncologist.2019-0189
M3 - Article
C2 - 31164455
AN - SCOPUS:85067407602
SN - 1083-7159
VL - 24
SP - 1174
EP - 1179
JO - Oncologist
JF - Oncologist
IS - 9
ER -