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 Bokemeyer; Axel 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

doi:10.1016/j.ejca.2024.114160

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 journal › Article › Academic › peer-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 language	English
Article number	114160
Number of pages	11
Journal	European Journal of Cancer
Volume	207
Early online date	18 Jun 2024
DOIs	https://doi.org/10.1016/j.ejca.2024.114160
Publication status	Published - Aug 2024

Keywords

Chemotherapy
Liver metastatic colorectal cancer
Prognostic value
Targeted therapy

Access to Document

10.1016/j.ejca.2024.114160

Cite this

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., ... de Gramont, A. (2024). Prognostic value of liver metastases in colorectal cancer treated by systemic therapy: An ARCAD pooled analysis. European Journal of Cancer, 207, Article 114160. https://doi.org/10.1016/j.ejca.2024.114160

@article{0ff6cc3474da420baf456518fc8f8c8f,

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.",

keywords = "Chemotherapy, Liver metastatic colorectal cancer, Prognostic value, Targeted therapy",

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

note = "Publisher Copyright: {\textcopyright} 2024 Elsevier Ltd",

year = "2024",

month = aug,

doi = "10.1016/j.ejca.2024.114160",

language = "English",

volume = "207",

journal = "European Journal of Cancer",

issn = "0959-8049",

publisher = "Elsevier Limited",

}

Cohen, R, Raeisi, M, Chibaudel, B, Shi, Q, Yoshino, T, Zalcberg, JR, Adams, R, Cremolini, C, Van Cutsem, E, Heinemann, V, Tabernero, J, Punt, CJA, Arnold, D, Hurwitz, HI, Douillard, JY, Venook, AP, Saltz, LB, Maughan, TS, Kabbinavar, F, Bokemeyer, C, Grothey, A, Mayer, RJ, Kaplan, R, Tebbutt, NC, Randolph Hecht, J, Giantonio, BJ, Díaz-Rubio, E, Sobrero, AF, Peeters, M, Koopman, M, Goldberg, RM, Andre, T & de Gramont, A 2024, 'Prognostic value of liver metastases in colorectal cancer treated by systemic therapy: An ARCAD pooled analysis', European Journal of Cancer, vol. 207, 114160. https://doi.org/10.1016/j.ejca.2024.114160

TY - JOUR

T1 - Prognostic value of liver metastases in colorectal cancer treated by systemic therapy

T2 - An ARCAD pooled analysis

AU - Cohen, Romain

AU - Raeisi, Morteza

AU - Chibaudel, Benoist

AU - Shi, Qian

AU - Yoshino, Takayuki

AU - Zalcberg, John R.

AU - Adams, Richard

AU - Cremolini, Chiara

AU - Van Cutsem, Eric

AU - Heinemann, Volker

AU - Tabernero, Josep

AU - Punt, Cornelis J.A.

AU - Arnold, Dirk

AU - Hurwitz, Herbert I.

AU - Douillard, Jean Yves

AU - Venook, Alan P.

AU - Saltz, Leonard B.

AU - Maughan, Timothy S.

AU - Kabbinavar, Fairooz

AU - Bokemeyer, Carsten

AU - Grothey, Axel

AU - Mayer, Robert J.

AU - Kaplan, Richard

AU - Tebbutt, Niall C.

AU - Randolph Hecht, J.

AU - Giantonio, Bruce J.

AU - Díaz-Rubio, Eduardo

AU - Sobrero, Alberto F.

AU - Peeters, Marc

AU - Koopman, Miriam

AU - Goldberg, Richard M.

AU - Andre, Thierry

AU - de Gramont, Aimery

PY - 2024/8

Y1 - 2024/8

N2 - 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.

AB - 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.

KW - Chemotherapy

KW - Liver metastatic colorectal cancer

KW - Prognostic value

KW - Targeted therapy

UR - http://www.scopus.com/inward/record.url?scp=85196270881&partnerID=8YFLogxK

U2 - 10.1016/j.ejca.2024.114160

DO - 10.1016/j.ejca.2024.114160

M3 - Article

C2 - 38896997

AN - SCOPUS:85196270881

SN - 0959-8049

VL - 207

JO - European Journal of Cancer

JF - European Journal of Cancer

M1 - 114160

ER -

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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this