He L, Cheng X, Gu Y, Zhou C, Li Q, Zhang B, Cheng X, Tu S
State Key Laboratory of Systems Medicine for Cancer, Department of Oncology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
Department of Laboratory Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
Clin Oncol (R Coll Radiol). 2025 Feb;38:103700. doi: 10.1016/j.clon.2024.103700. Epub 2024 Nov 26.
Programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors have shown limited effectiveness in patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Combining anti-angiogenesis inhibitors with PD-1 inhibitors has the potential to reverse the immunosuppressive tumour microenvironment, synergistically enhancing the anti-tumour immune response in MSS mCRC. The goal is to present real-world data that prove the clinical efficacy and safety of fruquintinib combined with PD-1 inhibitors in MSS mCRC.
We conducted a real-world retrospective study in patients with MSS mCRC who received treatment with fruquintinib combined with PD-1 inhibitors between May 2019 and March 2023 in our centre.
Seventy seven patients with MSS mCRC received fruquintinib combined with PD-1 inhibitors. In total, 5.2% of patients (4/77) achieved a partial response (PR), while 50.6% (39/77) had a stable disease (SD). Notably, three lesions achieving PR were all lung metastases and the overall disease control rate (DCR) reached 55.8% (43/77). Median progression-free survival (PFS) and overall survival (OS) reached 5.1 months (95% CI: 3.6-6.7) and 14.6 months (95% CI: 9.6-15.6), respectively. Multivariate Cox analysis showed that prior treatment without vascular endothelial growth factor (VEGF) inhibitors was significantly associated with PFS and OS (p < 0.05). Further analysis indicated that total- or polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) significantly decreased after treatment (P = 0.039), especially in the PR/SD group (P = 0.003). Most adverse events included abdominal pain, rash, oedema, diarrhoea, and immunotherapy-associated hypothyroidism, yet symptoms were controllable.
Our results provided additional evidence that patients with MSS mCRC could benefit from the combination of fruquintinib and PD-1 inhibitors, especially those with lung metastases or without prior treatment with VEGF inhibitors. The detection of MDSCs may be an immune indicator for predicting of the combined therapy.
程序性死亡蛋白1（PD-1）或程序性死亡配体1（PD-L1）抑制剂在微卫星稳定（MSS）的转移性结直肠癌（mCRC）患者中显示出有限的疗效。将抗血管生成抑制剂与PD-1抑制剂联合使用有可能逆转免疫抑制性肿瘤微环境，协同增强MSS mCRC中的抗肿瘤免疫反应。目的是提供真实世界数据，证明呋喹替尼联合PD-1抑制剂在MSS mCRC中的临床疗效和安全性。
我们对2019年5月至2023年3月期间在本中心接受呋喹替尼联合PD-1抑制剂治疗的MSS mCRC患者进行了一项真实世界回顾性研究。
77例MSS mCRC患者接受了呋喹替尼联合PD-1抑制剂治疗。总共有5.2%的患者（4/77）达到部分缓解（PR），而50.6%（39/77）病情稳定（SD）。值得注意的是，达到PR的三个病灶均为肺转移灶，总体疾病控制率（DCR）达到55.8%（43/77）。中位无进展生存期（PFS）和总生存期（OS）分别达到5.1个月（95%CI：3.6 - 6.7）和14.6个月（95%CI：9.6 - 15.6）。多因素Cox分析显示，既往未接受血管内皮生长因子（VEGF）抑制剂治疗与PFS和OS显著相关（p < 0.05）。进一步分析表明，治疗后总髓系来源抑制细胞或多形核髓系来源抑制细胞（PMN-MDSCs）显著减少（P = 0.039），尤其是在PR/SD组（P = 0.003）。大多数不良事件包括腹痛、皮疹、水肿、腹泻和免疫治疗相关的甲状腺功能减退，但症状可控。
我们的结果提供了额外的证据，表明MSS mCRC患者可从呋喹替尼和PD-1抑制剂的联合治疗中获益，尤其是那些有肺转移或既往未接受VEGF抑制剂治疗的患者。MDSCs的检测可能是预测联合治疗效果的一个免疫指标。
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