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

Romain Cohen, Morteza Raeisi*, Benoist Chibaudel, Qian Shi, Takayuki Yoshino, John R. Zalcberg, Richard Adams, Chiara Cremolini, Eric Van Cutsem, Volker Heinemann, Josep Tabernero, Cornelis J.A. Punt, Dirk Arnold, Herbert I. Hurwitz, Jean Yves Douillard, Alan P. Venook, Leonard B. Saltz, Timothy S. Maughan, Fairooz Kabbinavar, Carsten BokemeyerAxel Grothey, Robert J. Mayer, Richard Kaplan, Niall C. Tebbutt, J. Randolph Hecht, Bruce J. Giantonio, Eduardo Díaz-Rubio, Alberto F. Sobrero, Marc Peeters, Miriam Koopman, Richard M. Goldberg, Thierry Andre, Aimery de Gramont

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Article number114160
Number of pages11
JournalEuropean Journal of Cancer
Volume207
Early online date18 Jun 2024
DOIs
Publication statusPublished - Aug 2024

Keywords

  • Chemotherapy
  • Liver metastatic colorectal cancer
  • Prognostic value
  • Targeted therapy

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