Second-line treatment strategies for RAS wild-type colorectal cancer: A systematic review and Network Meta-analysis (NMA)

Dig Liver Dis. 2024 May;56(5):786-794. doi: 10.1016/j.dld.2023.07.013. Epub 2023 Aug 14.

Abstract

Background: The optimal strategy for second-line (IIL) treatment in KRAS wt metastatic colorectal cancer (mCRC) is not determined yet.

Methods: A random-effect NMA of phase II/III RCTs was conducted to evaluate IIL treatment for all-RAS wt mCRC, comparing anti-EGFR or anti-VEGF, and chemotherapy (CT).

Results: Overall, 11 RCTs (3613 patients) were included. In KRAS wt patients, PFS was improved with anti-VEGF (HR 0.43) and anti-EGFR (HR 0.63) vs CT. However, anti-VEGF based therapy had the highest likelihood of being ranked as the best treatment in terms of PFS (SUCRA 99.3%) and OS (SUCRA 99.4%). Bevacizumab-based treatment is most likely to be the best treatment in terms of PFS (SUCRA 89.1%) and OS (SUCRA 86.7%).

Conclusions: Second line treatment with anti-VEGF and anti-EGFR improved PFS in mCRC patients, however, anti-VEGF based therapy, particularly CT plus bevacizumab, is the best treatment according to SUCRA in terms of PFS and OS.

Keywords: Metastatic colorectal cancer; Network meta-analysis; RAS wt CRC; Second-line.

Publication types

  • Systematic Review
  • Meta-Analysis
  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bevacizumab* / therapeutic use
  • Clinical Trials, Phase II as Topic
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / pathology
  • ErbB Receptors* / antagonists & inhibitors
  • ErbB Receptors* / genetics
  • Humans
  • Network Meta-Analysis*
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Randomized Controlled Trials as Topic
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors

Substances

  • ErbB Receptors
  • Bevacizumab
  • Vascular Endothelial Growth Factor A
  • Proto-Oncogene Proteins p21(ras)