Liver metastases do not predict resistance to the addition of atezolizumab to first-line FOLFOXIRI plus bevacizumab in proficient MMR metastatic colorectal cancer: a secondary analysis of the AtezoTRIBE study

IF 8.3 2区医学 Q1 ONCOLOGY ESMO Open Pub Date : 2025-02-01 Epub Date: 2025-02-04 DOI:10.1016/j.esmoop.2025.104135

C. Antoniotti , M. Carullo , D. Rossini , F. Pietrantonio , L. Salvatore , S. Lonardi , S. Tamberi , C. Sciortino , V. Conca , M.A. Calegari , P. Ciracì , E. Tamburini , F. Bergamo , C. Boccaccio , A. Passardi , G. Ritorto , C. Ugolini , G. Aprile , J. Galon , C. Cremolini

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Abstract

Background

Liver metastases (LMs) are related to poor efficacy of immune checkpoint inhibitor (ICI)-containing therapies. In the AtezoTRIBE trial, Immunoscore-Immune-Checkpoint (immunoscore-IC) was a predictor of benefit from atezolizumab in mismatch repair-proficient (pMMR) metastatic colorectal cancer (mCRC).

Patients and methods

In pMMR patients enrolled in the AtezoTRIBE study, we investigated the association of LMs with immune-related biomarkers and treatment outcomes, and the predictive role of immunoscore-IC in the LMs group.

Results

Out of 202 pMMR patients, 151 (75%) had LMs. No differences in immune-related features were observed according to the presence or not of LMs, except for a lower prevalence of tumour-infiltrating lymphocytes-high tumours in the LMs group (33% versus 52%, P = 0.03). Worse outcomes were observed among patients with LMs [progression-free survival (PFS), P = 0.002; overall survival (OS), P = 0.011], also in multivariable models. The effect of adding atezolizumab to FOLFOXIRI/bevacizumab was independent from LMs in terms of PFS (P_int = 0.990) and OS (P_int = 0.800). Among patients with pMMR mCRC and LMs, those with immunoscore-IC-high but not those with immunoscore-IC-low tumours achieved benefit from atezolizumab, though in the absence of a statistically significant interaction effect (P_int for PFS and OS = 0.166 and 0.473, respectively).

Conclusions

LMs are associated with poor prognosis in pMMR mCRC and do not predict resistance to the addition of atezolizumab to FOLFOXIRI/bevacizumab. Immunoscore-IC seems to retain its predictive impact also among patients with LMs.

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肝转移不能预测MMR转移性结直肠癌患者在一线FOLFOXIRI +贝伐单抗的基础上加用atezolizumab的耐药性：AtezoTRIBE研究的二次分析

肝转移（LMs）与含免疫检查点抑制剂（ICI）的治疗效果差有关。在AtezoTRIBE试验中，免疫评分-免疫检查点（免疫评分- ic）是atezolizumab在错配修复熟练（pMMR）转移性结直肠癌（mCRC）中获益的预测指标。患者和方法在纳入AtezoTRIBE研究的pMMR患者中，我们研究了LMs与免疫相关生物标志物和治疗结果的相关性，以及免疫评分- ic在LMs组中的预测作用。结果202例pMMR患者中，151例（75%）发生LMs。除了LMs组肿瘤浸润性淋巴细胞高肿瘤的患病率较低（33%对52%，P = 0.03）外，LMs组的免疫相关特征没有差异。LMs患者的预后较差[无进展生存期（PFS）， P = 0.002；总生存期（OS）， P = 0.011]，在多变量模型中也是如此。在FOLFOXIRI/bevacizumab中加入atezolizumab的影响在PFS （Pint = 0.990）和OS （Pint = 0.800）方面与LMs无关。在pMMR mCRC和LMs患者中，那些免疫评分ic高而非免疫评分ic低的肿瘤患者从atezolizumab中获益，尽管没有统计学上显著的相互作用效应（PFS和OS的Pint分别= 0.166和0.473）。结论slm与pMMR mCRC的不良预后相关，并且不能预测对FOLFOXIRI/贝伐单抗加用atezolizumab的耐药性。免疫评分- ic似乎在LMs患者中也保留了其预测作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ESMO Open Medicine-Oncology

CiteScore

11.70

自引率

2.70%

发文量

255

审稿时长

10 weeks

期刊介绍： ESMO Open is the online-only, open access journal of the European Society for Medical Oncology (ESMO). It is a peer-reviewed publication dedicated to sharing high-quality medical research and educational materials from various fields of oncology. The journal specifically focuses on showcasing innovative clinical and translational cancer research. ESMO Open aims to publish a wide range of research articles covering all aspects of oncology, including experimental studies, translational research, diagnostic advancements, and therapeutic approaches. The content of the journal includes original research articles, insightful reviews, thought-provoking editorials, and correspondence. Moreover, the journal warmly welcomes the submission of phase I trials and meta-analyses. It also showcases reviews from significant ESMO conferences and meetings, as well as publishes important position statements on behalf of ESMO. Overall, ESMO Open offers a platform for scientists, clinicians, and researchers in the field of oncology to share their valuable insights and contribute to advancing the understanding and treatment of cancer. The journal serves as a source of up-to-date information and fosters collaboration within the oncology community.