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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
背景：肝脏是结直肠癌（CRC）中最常见的转移部位。本研究旨在评估不同治疗路线的非肝转移（NLM）转移性CRC患者与肝转移（LM）患者相比的反应率和生存结果。
方法：分析了来自ARCADCRC数据库的26项试验中的17,924例mCRC患者。根据不同治疗组是否存在LM进行分析：单独化疗（CT），CT+抗VEGF,KRAS野生型肿瘤的CT+抗EGFR,在第一线(1L)和第二线(2L)内，和纳入接受三氟尿苷/替吡草定或瑞戈非尼或安慰剂治疗的三线(≥3L)试验的患者.终点是总生存期（OS），无进展生存期（PFS），总体反应率（ORR）。
结果：在17,924名患者中，14,066人患有LM（30.6％仅肝脏受累，69.4％患有肝脏和其他转移部位），3858例患者患有NLM。在单独CT和CT+抗VEGF亚组中，NLM患者在1L和2L设置下表现出更好的OS和PFS。然而,在CT+抗EGFR1L和2L亚组中，NLM和LM患者的OS和PFS无显著差异。在≥3L的亚组中，在NLM患者中观察到更好的OS和PFS。在1L治疗的所有队列中，LM患者的ORR高于NLM患者，仅在2L治疗的抗EGFR队列中
结论：LM是mCRC从1L增加到≥3L的不良预后因素，除了1L和2L患者接受CT+抗EGFR。这些数据证明在未来的不可切除的mCRC患者的试验中使用LM作为分层因子是合理的。
方法：分析了来自ARCADCRC数据库的26项试验中的17,924例mCRC患者。根据不同治疗组是否存在LM进行分析：单独化疗（CT），CT+抗VEGF,KRAS野生型肿瘤的CT+抗EGFR,在第一线(1L)和第二线(2L)内，和纳入接受三氟尿苷/替吡草定或瑞戈非尼或安慰剂治疗的三线(≥3L)试验的患者.终点是总生存期（OS），无进展生存期（PFS），总体反应率（ORR）。
结果：在17,924名患者中，14,066人患有LM（30.6％仅肝脏受累，69.4％患有肝脏和其他转移部位），3858例患者患有NLM。在单独CT和CT+抗VEGF亚组中，NLM患者在1L和2L设置下表现出更好的OS和PFS。然而,在CT+抗EGFR1L和2L亚组中，NLM和LM患者的OS和PFS无显著差异。在≥3L的亚组中，在NLM患者中观察到更好的OS和PFS。在1L治疗的所有队列中，LM患者的ORR高于NLM患者，仅在2L治疗的抗EGFR队列中
结论：LM是mCRC从1L增加到≥3L的不良预后因素，除了1L和2L患者接受CT+抗EGFR。这些数据证明在未来的不可切除的mCRC患者的试验中使用LM作为分层因子是合理的。
