Zhao Wensi, Chen Yuan, Xiao Jiping, Tang Ze, Wang Li, Ren Yiping, Chen Yongshun
Department of Oncology, Renmin Hospital of Wuhan University Wuhan, Hubei, China.
Department of Oncology, Qianjiang Central Hospital of Yangtze University Qianjiang, Hubei, China.
Am J Cancer Res. 2024 Nov 15;14(11):5351-5364. doi: 10.62347/XKUJ3012. eCollection 2024.
Primary analysis of the open-label, single-arm, phase II RENMIN-215 trial (primary data cutoff date: July 10, 2023) showed promising efficacy and tolerable safety with tislelizumab plus fruquintinib and fecal microbiota transplantation (FMT) in patients with refractory microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Here, we reported updated survival and safety results with a median follow-up of 34.0 months (data cut-off May 20, 2024), as well as patient-reported outcomes and laboratory analysis. Twenty patients with MSS mCRC resistant or refractory to at least second-line therapy were enrolled and received tislelizumab plus fruquintinib and FMT. The primary endpoint was progression-free survival. Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate, safety, health-related quality of life questionnaire and exploratory laboratory tests. In addition, 94 mCRC patients who received third-line or above immunotherapy in real world were screened for propensity score matching (PSM) analysis to compare efficacy. Our results showed that the median OS was 13.7 months (95% CI, 9.3-17.7), and the ORR was 20.0% (95% CI, 5.7-43.7). After PSM, the median OS benefit of the study regimen remained statistically significant (HR = 0.26; 95% CI, 0.07-0.95; = 0.042). Patients with primary tumor surgery had better clinical outcomes. No new safety concerns were detected. Seven (35.0%) patients had one or more grade 3 treatment-related adverse events. The majority of patients had improved or stable global health status (GHS). Median time to deterioration for GHS was 7.7 months. Peripheral blood lymphocyte analysis showed that increased gamma-delta 2 T cells were positively associated with improved response and survival. To conclude, the updated results provide further evidence of sustained antitumor activity of tislelizumab plus fruquintinib and FMT in heavily pretreated MSS mCRC patients with a consistent safety profile.
开放标签、单臂、II期RENMIN-215试验（主要数据截止日期：2023年7月10日）的初步分析显示，替雷利珠单抗联合呋喹替尼及粪便微生物群移植（FMT）治疗难治性微卫星稳定（MSS）转移性结直肠癌（mCRC）患者具有良好的疗效和可耐受的安全性。在此，我们报告了中位随访34.0个月（数据截止日期为2024年5月20日）后的更新生存和安全性结果，以及患者报告的结局和实验室分析。20例对至少二线治疗耐药或难治的MSS mCRC患者入组并接受替雷利珠单抗联合呋喹替尼及FMT治疗。主要终点为无进展生存期。次要终点包括总生存期（OS）、客观缓解率（ORR）、疾病控制率、安全性、健康相关生活质量问卷和探索性实验室检查。此外，对94例在现实世界中接受三线或以上免疫治疗的mCRC患者进行倾向评分匹配（PSM）分析以比较疗效。我们的结果显示，中位OS为13.7个月（95%CI，9.3 - 17.7），ORR为20.0%（95%CI，5.7 - 43.7）。PSM后，研究方案的中位OS获益仍具有统计学意义（HR = 0.26；95%CI，0.07 - 0.95；P = 0.042）。接受原发性肿瘤手术的患者临床结局更好。未发现新的安全问题。7例（35.0%）患者发生1种或更多种3级治疗相关不良事件。大多数患者的整体健康状况（GHS）改善或稳定。GHS恶化的中位时间为7.7个月。外周血淋巴细胞分析显示，γδ2 T细胞增加与反应改善和生存呈正相关。总之，更新后的结果进一步证明了替雷利珠单抗联合呋喹替尼及FMT在经过大量预处理的MSS mCRC患者中具有持续的抗肿瘤活性，且安全性特征一致。
