PMID- 32728393
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220415
IS  - 1758-8340 (Print)
IS  - 1758-8359 (Electronic)
IS  - 1758-8340 (Linking)
VI  - 12
DP  - 2020
TI  - Efficacy and safety of regorafenib as beyond second-line therapy in patients with 
      metastatic colorectal cancer: an adjusted indirect meta-analysis and systematic 
      review.
PG  - 1758835920940932
LID - 10.1177/1758835920940932 [doi]
LID - 1758835920940932
AB  - BACKGROUND: The evidence base for optimum third-line therapy for metastatic 
      colorectal cancer (mCRC) is not conclusive. Recent studies have demonstrated the 
      efficacy of regorafenib as third-line therapy in mCRC. This indirect 
      meta-analysis compared the efficacy and safety of regorafenib with other 
      available third-line therapies for mCRC. METHODS: A literature search for 
      randomized controlled trials (RCTs) was conducted in PubMed, Embase, and Cochrane 
      Library for studies evaluating the efficacy and safety of fruquintinib, 
      regorafenib, TAS-102, and nintedanib as third-line therapies in patients with 
      mCRC. Overall survival (OS) and progression-free survival (PFS) were the primary 
      outcomes, while objective response rate (ORR) and safety were the secondary 
      outcomes. Hazard ratio (HR) and relative risk (RR) with their respective 95% 
      confidence interval (CI) were used for analysis of survival, clinical response, 
      and safety data. An adjusted indirect meta-analysis with placebo as the common 
      comparator was performed. RESULTS: We identified eight RCTs comparing regorafenib 
      (two studies), fruquintinib (two studies), TAS-102 (three studies), and 
      nintedanib (one study) against placebo. The OS with regorafenib was significantly 
      better when compared with nintedanib (HR = 0.66; 95% CI: 0.45, 0.95, p = 0.02) 
      but was similar to that of fruquintinib (HR = 1.01; 95% CI: 0.67, 1.52, p = 0.94) 
      and TAS-102 (HR = 0.97; 95% CI: 0.68, 1.38, p = 0.88). The PFS and ORR for 
      regorafenib were slightly better than those of TAS-102 (PFS: HR = 0.86, 95% CI: 
      0.54, 1.37, p = 0.5; ORR: RR = 1.13, 95% CI: 0.11, 11.05, p = 0.92) and 
      nintedanib (PFS: HR = 0.68, 95% CI: 0.42, 1.10, p = 0.12; ORR: not reported) but 
      were lower than those for fruquintinib (PFS: HR = 1.53, 95% CI: 0.93, 2.52, 
      p = 0.08; ORR: RR = 0.68269, 95% CI: 0.045, 10.32, p = 0.79). Safety analysis 
      showed that the RR of adverse events (AEs) was lesser in patients treated with 
      regorafenib in comparison with that in patients treated with fruquintinib, but 
      was similar to that in patients treated with nintedanib and TAS-102. CONCLUSION: 
      Regorafenib has efficacy similar to that of TAS-102 and better safety when 
      compared with fruquintinib. Considering the mechanism of action of regorafenib, 
      which targets multiple factors in the angiogenic pathway, it could be an ideal 
      option for treatment in the beyond second-line setting.
CI  - (c) The Author(s), 2020.
FAU - Wu, Yinying
AU  - Wu Y
AD  - Department of Medical Oncology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
FAU - Fan, Yangwei
AU  - Fan Y
AD  - Department of Medical Oncology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
FAU - Dong, Danfeng
AU  - Dong D
AD  - Department of Medical Oncology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
FAU - Dong, Xuyuan
AU  - Dong X
AD  - Department of Medical Oncology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
FAU - Hu, Yuan
AU  - Hu Y
AD  - Department of Medical Oncology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
FAU - Shi, Yu
AU  - Shi Y
AD  - Department of Medical Oncology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
FAU - Jing, Jiayu
AU  - Jing J
AD  - Department of Medical Oncology, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
FAU - Li, Enxiao
AU  - Li E
AUID- ORCID: 0000-0003-3909-211X
AD  - Department of Medical Oncology, Xi'an Jiaotong University, 277 Yanta West Road, 
      Xi'an, Shaanxi 710061, China.
LA  - eng
PT  - Journal Article
DEP - 20200715
PL  - England
TA  - Ther Adv Med Oncol
JT  - Therapeutic advances in medical oncology
JID - 101510808
PMC - PMC7364795
OTO - NOTNLM
OT  - fruquintinib
OT  - meta-analysis
OT  - metastatic colorectal cancer
OT  - nintedanib
OT  - regorafenib
COIS- Conflict of interest statement: The authors declare that there is no conflict of 
      interest.
EDAT- 2020/07/31 06:00
MHDA- 2020/07/31 06:01
PMCR- 2020/07/15
CRDT- 2020/07/31 06:00
PHST- 2019/10/17 00:00 [received]
PHST- 2020/06/12 00:00 [accepted]
PHST- 2020/07/31 06:00 [entrez]
PHST- 2020/07/31 06:00 [pubmed]
PHST- 2020/07/31 06:01 [medline]
PHST- 2020/07/15 00:00 [pmc-release]
AID - 10.1177_1758835920940932 [pii]
AID - 10.1177/1758835920940932 [doi]
PST - epublish
SO  - Ther Adv Med Oncol. 2020 Jul 15;12:1758835920940932. doi: 
      10.1177/1758835920940932. eCollection 2020.