Gao Zhao, Wang Xiaoyan, Song Tao, Wu Shikai, Jin Xuan
Department of Medical Oncology, Peking University First Hospital, No.8, Xishiku Street, Beijing, 100034, China.
Department of Pharmacy, Jilin Cancer Hospital, Changchun, 130012, Jilin, China.
Sci Rep. 2025 Aug 9;15(1):29170. doi: 10.1038/s41598-025-13701-0.
Patients diagnosed with microsatellite stable (MSS) metastatic colorectal cancer (mCRC) typically have an immunosuppressive tumor microenvironment, which leads to a low response rate when treated with immunotherapy. Some studies indicate that chemotherapy and anti-angiogenic therapy could potentially improve the responsiveness of these patients to immunotherapy. Therefore, this study is designed to assess the effectiveness and safety of combining chemotherapy with bevacizumab and anti-PD-1 immunotherapy as a second-line treatment option for MSS mCRC. A retrospective analysis was conducted on patients diagnosed with MSS mCRC at Peking University First Hospital and Jilin Cancer Hospital from January 2020 to December 2024. Patients received second-line chemotherapy in combination with bevacizumab and anti-PD-1 immunotherapy. Progression-free survival (PFS), overall survival (OS), disease control rate (DCR), objective response rate (ORR), and treatment-related adverse reactions were collected. Biomarker analysis was performed to identify potential predictors of a favorable treatment response. Between January 2021 and December 2024, 29 patients were enrolled. Five patients (17.2%) achieved a partial response (PR), and 18 patients (62.1%) had stable disease. The median follow-up period was 13.3 months. The ORR was 17.2%, and the DCR was 79.3%. The median PFS was 7.8 months, and the median OS was 28.8 months. The most common treatment-related adverse events (TRAEs) of all grades were anemia (18/29, 62.1%), leukopenia (12/29, 41.4%), and hand-foot syndrome (10/29, 34.5%). The most frequent grade 3 or 4 TRAEs were anemia (2/29, 6.9%) and elevated triglycerides (1/29, 3.4%). No grade 5 adverse events occurred. Dynamic changes in the Lymphocyte-to-Monocyte Ratio (LMR), Systemic Immune-Inflammation Index (SII), and Platelet-to-Inflammatory Index (PIV) before and after treatment could predict the efficacy of immune combination therapy. In the biomarker exploration, multiple immunohistochemical analyses indicated better tumor immune microenvironment cell infiltration in the PFS-long (≥ 16 weeks) group compared to the PFS-short group. Chemotherapy combined with bevacizumab and anti-PD-1 immunotherapy has demonstrated promising efficacy in the treatment of MSS mCRC, with manageable adverse reactions. Exploratory biomarker assessment analysis showed that hematological dynamic changes and tumor immune microenvironment cell infiltration may predict the efficacy of immune combination therapy.
被诊断为微卫星稳定（MSS）转移性结直肠癌（mCRC）的患者通常具有免疫抑制性肿瘤微环境，这导致其接受免疫治疗时的缓解率较低。一些研究表明，化疗和抗血管生成治疗可能会提高这些患者对免疫治疗的反应性。因此，本研究旨在评估化疗联合贝伐单抗和抗PD-1免疫治疗作为MSS mCRC二线治疗方案的有效性和安全性。对2020年1月至2024年12月在北京大学第一医院和吉林省肿瘤医院被诊断为MSS mCRC的患者进行了回顾性分析。患者接受二线化疗联合贝伐单抗和抗PD-1免疫治疗。收集无进展生存期（PFS）、总生存期（OS）、疾病控制率（DCR）、客观缓解率（ORR）及治疗相关不良反应。进行生物标志物分析以确定良好治疗反应的潜在预测因素。2021年1月至2024年12月期间，共纳入29例患者。5例患者（17.2%）获得部分缓解（PR），18例患者（62.1%）疾病稳定。中位随访期为13.3个月。ORR为17.2%，DCR为79.3%。中位PFS为7.8个月，中位OS为28.8个月。所有级别的最常见治疗相关不良事件（TRAEs）为贫血（18/29，62.1%）、白细胞减少（12/29，41.4%）和手足综合征（10/29，34.5%）。最常见的3级或4级TRAEs为贫血（2/29，6.9%）和甘油三酯升高（1/29，3.4%）。未发生5级不良事件。治疗前后淋巴细胞与单核细胞比值（LMR）、全身免疫炎症指数（SII）和血小板与炎症指数（PIV）的动态变化可预测免疫联合治疗的疗效。在生物标志物探索中，多项免疫组化分析表明，与PFS短的组相比，PFS长（≥16周）组的肿瘤免疫微环境细胞浸润情况更好。化疗联合贝伐单抗和抗PD-1免疫治疗在MSS mCRC治疗中显示出有前景的疗效，且不良反应可控。探索性生物标志物评估分析表明，血液学动态变化和肿瘤免疫微环境细胞浸润可能预测免疫联合治疗的疗效。
