Inosine enhances the efficacy of immune-checkpoint inhibitors in advanced solid tumors: A randomized, controlled, Phase 2 study.

Autor: Zhao H; 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., Zhang W; Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China., Lu Y; Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China., Dong Y; Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China., He Z; Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China., Zhen H; Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China., Li Q; Department of Oncology, Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China.
Jazyk: angličtina
Zdroj: Cancer medicine [Cancer Med] 2024 Sep; Vol. 13 (17), pp. e70143.
DOI: 10.1002/cam4.70143
Abstrakt: 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.
(© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje