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


Authors: Cohen, R.; Raeisi, M.; Chibaudel, B.; Shi, Q.; Yoshino, T.; Zalcberg, J. R.; Adams, R.; Cremolini, C.; Van Cutsem, E.; Heinemann, V.; Tabernero, J.; Punt, C. J. A.; Arnold, D.; Hurwitz, H. I.; Douillard, J. Y.; Venook, A. P.; Saltz, L. B.; Maughan, T. S.; Kabbinavar, F.; Bokemeyer, C.; Grothey, A.; Mayer, R. J.; Kaplan, R.; Tebbutt, N. C.; Randolph Hecht, J.; Giantonio, B. J.; Díaz-Rubio, E.; Sobrero, A. F.; Peeters, M.; Koopman, M.; Goldberg, R. M.; Andre, T.; de Gramont, A.
Article Title: Prognostic value of liver metastases in colorectal cancer treated by systemic therapy: An ARCAD pooled analysis
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. © 2024 Elsevier Ltd
Keywords: treatment response; aged; major clinical study; overall survival; placebo; cancer combination chemotherapy; systemic therapy; chemotherapy; lymph node metastasis; progression free survival; cohort analysis; data base; wild type; irinotecan; monoclonal antibody; lung metastasis; targeted therapy; oncogene k ras; oxaliplatin; peritoneum metastasis; vasculotropin antibody; epidermal growth factor receptor antibody; prognostic value; randomized controlled trial (topic); molecularly targeted therapy; second-line treatment; overall response rate; first-line treatment; chemoimmunotherapy; cancer prognosis; capecitabine plus oxaliplatin; regorafenib; colorectal liver metastasis; human; male; female; article; prognostic assessment; tipiracil plus trifluridine; liver metastatic colorectal cancer; third-line treatment
Journal Title: European Journal of Cancer
Volume: 207
ISSN: 0959-8049
Publisher: Elsevier Inc.  
Date Published: 2024-08-01
Start Page: 114160
Language: English
DOI: 10.1016/j.ejca.2024.114160
PUBMED: 38896997
PROVIDER: scopus
DOI/URL:
Notes: Article -- Source: Scopus
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  1. Leonard B Saltz
    791 Saltz