Sommerhäuser Greta, Karthaus Meinolf, Kurreck Annika, Ballhausen Alexej, Meyer-Knees Johanna W, Fruehauf Stefan, Graeven Ullrich, Mueller Lothar, Koenig Alexander O, Weikersthal Ludwig Fischer V, Goekkurt Eray, Haas Siegfried, Stahler Arndt, Heinemann Volker, Held Swantje, Alig Annabel H S, Kasper-Virchow Stefan, Stintzing Sebastian, Trarbach Tanja, Modest Dominik P
Department of Hematology, Oncology, and Cancer Immunology (CVK/CCM), Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Department of Hematology, Oncology, and Palliative Care, Klinikum Neuperlach/Klinikum Harlaching, Munich, Germany.
Int J Cancer. 2024 Mar 1;154(5):863-872. doi: 10.1002/ijc.34760. Epub 2023 Oct 15.
Despite molecular selection, patients (pts) with RAS wildtype mCRC represent a heterogeneous population including diversity in metastatic spread. We investigated metastatic patterns for their prognostic and predictive impact on maintenance therapy with 5-fluorouracil/folinic acid ± panitumumab. The study population was stratified according to (1) number of involved metastatic sites (single vs multiple organ metastasis), liver-limited disease vs (2) liver metastasis plus one additional site, and (3) vs liver metastasis plus ≥two additional sites. Kaplan-Meier method and Cox regressions were used to correlate efficacy endpoints. Single organ metastasis was observed in 133 pts (53.6%) with 102 pts (41.1%) presenting with liver-limited disease, while multiple organ metastases were reported in 114 pts (46.0). Multiple compared to single organ metastases were associated with less favorable PFS (HR 1.48, 95% CI 1.13-1.93; P = .004) and OS (HR 1.37, 95% CI 0.98-1.93; P = .068) of maintenance therapy. While metastatic spread involving one additional extrahepatic site was not associated with clearly impaired survival compared to liver-limited disease, pts with liver metastasis plus ≥two additional sites demonstrated less favorable PFS (HR 1.92, 95% CI 1.30-2.83; P < .001), and OS (HR 2.38, 95% CI 1.51-3.76; P < .001) of maintenance therapy. Pmab-containing maintenance therapy appeared active in both pts with multiple (HR 0.58; 95% CI, 0.39-0.86; P = .006) as well as to a lesser numerical extent in pts with single organ metastasis (HR 0.83; 95% CI, 0.57-1.21; P = .332; Interaction P = .183). These data may support clinical decisions when EGFR-based maintenance therapy is considered.
尽管进行了分子筛选，但RAS野生型转移性结直肠癌（mCRC）患者仍为异质性群体，包括转移扩散的多样性。我们研究了转移模式对5-氟尿嘧啶/亚叶酸钙±帕尼单抗维持治疗的预后和预测影响。研究人群根据以下因素进行分层：（1）受累转移部位的数量（单器官转移与多器官转移），肝局限性疾病与（2）肝转移加一个额外部位，以及（3）肝转移加≥两个额外部位。采用Kaplan-Meier法和Cox回归分析来关联疗效终点。133例患者（53.6%）出现单器官转移，其中102例患者（41.1%）为肝局限性疾病，而114例患者（46.0%）报告有多器官转移。与单器官转移相比，多器官转移与维持治疗的无进展生存期（PFS）较差相关（风险比[HR]1.48，95%置信区间[CI]1.13-1.93；P = 0.004），总生存期（OS）也较差（HR 1.37，95% CI 0.98-1.93；P = 0.068）。与肝局限性疾病相比，涉及一个额外肝外部位的转移扩散与生存期明显受损无关，但肝转移加≥两个额外部位的患者维持治疗的PFS较差（HR 1.92，95% CI 1.30-2.83；P < 0.001），OS也较差（HR 2.38，95% CI 1.51-3.76；P < 0.001）。含帕尼单抗的维持治疗在多器官转移患者中似乎有效（HR 0.58；95% CI，0.39-0.86；P = 0.006），在单器官转移患者中的数值效应较小（HR 0.83；95% CI，0.57-1.21；P = 0.332；交互作用P = 0.183）。在考虑基于表皮生长因子受体（EGFR）的维持治疗时，这些数据可能有助于临床决策。
