肌苷增强免疫检查点抑制剂治疗晚期实体瘤的疗效：一项随机、对照、Ⅱ期研究。
Inosine enhances the efficacy of immune-checkpoint inhibitors in advanced solid tumors: A randomized, controlled, Phase 2 study.
机构信息
Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China.
Internal Medicine Department, People's Hospital of Shen chi County, Shanxi, People's Republic of China.
出版信息
Cancer Med. 2024 Sep;13(17):e70143. doi: 10.1002/cam4.70143.
BACKGROUND
This study aimed to evaluate whether inosine enhances the efficacy of immune-checkpoint inhibitors in human malignant solid tumors.
METHODS
This single-center, prospective, randomized, open-label study was conducted, from January 2021 to December 2022, in Beijing Friendship Hospital, Capital Medical University, and participants were randomly assigned (1:1) to either the inosine (trial) or non-inosine (control) group that received inosine (dosage: 0.2 g, three times/day) + PD-1/PD-L1 inhibitor or only PD-1/PD-L1 inhibitor ± targeted ± chemotherapy, respectively. Efficacy was assessed every 6 weeks (i.e., after every two-three treatment cycles). The primary endpoint was the objective response rate (ORR); the secondary endpoints were disease control rate, overall survival (OS), and progression-free survival (PFS). The trial was registered at ClinicalTrials.gov (NCT05809336).
RESULTS
Among the 172 participants with advanced malignant solid tumors, 86 each were assigned to the inosine and non-inosine groups, wherein the median PFS (95% CI) was 7.00 (5.31-8.69) and 4.40 (3.10-5.70) months, respectively (hazard ratio [HR] 0.63; 95% CI 0.44-0.90, p = 0.011), and the ORR was 26.7% and 15.1%, respectively (p = 0.061). In the inosine and non-inosine groups, the median OS was not reached and was 29.67 (95% CI 17.40-41.94) months, respectively (HR 1.05 [95% CI 0.59-1.84], p = 0.874). Compared with the non-inosine group, the median PFS and ORR of the inosine group were significantly prolonged and improved in the multiple exploratory subgroup analyses. The safety analysis showed that Grades 3 and 4 adverse reactions occurred in 25 (29%) and 31 (36%) patients in the inosine and non-inosine groups, respectively, and tended to decrease in the inosine group compared with the non-inosine group.
CONCLUSION
Inosine had a tendency to enhance the efficacy of immune-checkpoint inhibitors and reduced immunotherapy-related adverse reactions.
背景
本研究旨在评估肌苷是否能提高免疫检查点抑制剂在人类恶性实体肿瘤中的疗效。
方法
这是一项单中心、前瞻性、随机、开放标签的研究，于 2021 年 1 月至 2022 年 12 月在北京友谊医院进行，参与者被随机分配（1:1）至肌苷组（试验组）或非肌苷组（对照组），分别接受肌苷（剂量：0.2 g，每日 3 次）+PD-1/PD-L1 抑制剂或仅 PD-1/PD-L1 抑制剂±靶向±化疗。每 6 周（即每两个治疗周期后）评估疗效。主要终点是客观缓解率（ORR）；次要终点是疾病控制率、总生存期（OS）和无进展生存期（PFS）。该试验在 ClinicalTrials.gov 注册（NCT05809336）。
结果
在 172 名患有晚期恶性实体肿瘤的参与者中，86 名被分配至肌苷组和非肌苷组，其中中位 PFS（95%CI）分别为 7.00（5.31-8.69）和 4.40（3.10-5.70）个月（风险比[HR]0.63；95%CI 0.44-0.90，p=0.011），ORR 分别为 26.7%和 15.1%（p=0.061）。在肌苷组和非肌苷组中，中位 OS 均未达到，分别为 29.67（95%CI 17.40-41.94）个月（HR 1.05 [95%CI 0.59-1.84]，p=0.874）。与非肌苷组相比，在多项探索性亚组分析中，肌苷组的中位 PFS 和 ORR 均显著延长和改善。安全性分析显示，肌苷组和非肌苷组分别有 25（29%）和 31（36%）例患者出现 3 级和 4 级不良反应，肌苷组与非肌苷组相比，不良反应发生率有降低的趋势。
结论
肌苷有增强免疫检查点抑制剂疗效的趋势，并降低免疫治疗相关不良反应。
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