Prognostic value of liver metastases in colorectal cancer treated by systemic therapy: An ARCAD pooled analysis

Eur J Cancer. 2024 Aug:207:114160. doi: 10.1016/j.ejca.2024.114160. Epub 2024 Jun 10.

Abstract

Background: The liver is the most frequent site of metastases in colorectal cancer (CRC). This study aimed to assess the response rate and survival outcomes in metastatic CRC patients with non-liver metastases (NLM) compared to those with liver metastases (LM) across different lines of treatment.

Methods: A total of 17,924 mCRC patients included in 26 trials from the ARCAD CRC database were analyzed. The analysis was conducted based on the presence or absence of LM across different treatment groups: chemotherapy (CT) alone, CT + anti-VEGF, CT + anti-EGFR in KRAS wild-type tumors, within the first-line (1 L) and second-line (2 L), and patients enrolled in third-line (≥3 L) trials treated with trifluridine/tipiracil or regorafenib or placebo. The endpoints were overall survival (OS), progression-free survival (PFS), and overall response rate (ORR).

Results: Out of the 17,924 patients, 14,066 had LM (30.6 % with only liver involvement and 69.4 % with liver and other metastatic sites), while 3858 patients had NLM. In the CT alone and CT + anti-VEGF subgroups, NLM patients showed better OS and PFS in the 1 L and 2 L settings. However, in the CT + anti-EGFR 1 L and 2 L subgroups, there was no significant difference in OS and PFS between NLM and LM patients. In the ≥ 3 L subgroups, better OS and PFS were observed in NLM patients. ORRs were higher in LM patients than in NLM patients across all cohorts treated in the 1 L and only in the anti-EGFR cohort in the 2 L.

Conclusion: LM is a poor prognostic factor for mCRC increasing from 1 L to ≥ 3 L except for patients in 1 L and 2 L receiving CT+anti-EGFR. These data justify using LM as a stratification factor in future trials for patients with unresectable mCRC.

Keywords: Chemotherapy; Liver metastatic colorectal cancer; Prognostic value; Targeted therapy.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / mortality
  • Colorectal Neoplasms* / pathology
  • Drug Combinations
  • Female
  • Humans
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / mortality
  • Liver Neoplasms* / secondary
  • Male
  • Middle Aged
  • Phenylurea Compounds / therapeutic use
  • Prognosis
  • Progression-Free Survival
  • Pyridines / therapeutic use
  • Pyrrolidines
  • Thymine / therapeutic use
  • Trifluridine / therapeutic use

Substances

  • trifluridine tipiracil drug combination
  • regorafenib
  • Pyridines
  • Trifluridine
  • Phenylurea Compounds
  • Thymine
  • Drug Combinations
  • Pyrrolidines