Inosine enhances the efficacy of immune‐checkpoint inhibitors in advanced solid tumors: A randomized, controlled, Phase 2 study
Abstract 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 Hospi...
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Wiley
2024-09-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.70143 |
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| author | Haiqing Zhao Wei Zhang Yuting Lu Yin Dong Zhihao He Hongchao Zhen Qin Li |
| author_facet | Haiqing Zhao Wei Zhang Yuting Lu Yin Dong Zhihao He Hongchao Zhen Qin Li |
| author_sort | Haiqing Zhao |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-2a42f36d77c74567a680cf978bc30f38 |
| institution | Kabale University |
| issn | 2045-7634 |
| language | English |
| publishDate | 2024-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-2a42f36d77c74567a680cf978bc30f382025-02-07T09:08:08ZengWileyCancer Medicine2045-76342024-09-011317n/an/a10.1002/cam4.70143Inosine enhances the efficacy of immune‐checkpoint inhibitors in advanced solid tumors: A randomized, controlled, Phase 2 studyHaiqing Zhao0Wei Zhang1Yuting Lu2Yin Dong3Zhihao He4Hongchao Zhen5Qin Li6Department of Oncology, Beijing Friendship Hospital Capital Medical University Beijing People's Republic of ChinaDepartment of Oncology, Beijing Friendship Hospital Capital Medical University Beijing People's Republic of ChinaDepartment of Oncology, Beijing Friendship Hospital Capital Medical University Beijing People's Republic of ChinaDepartment of Oncology, Beijing Friendship Hospital Capital Medical University Beijing People's Republic of ChinaDepartment of Oncology, Beijing Friendship Hospital Capital Medical University Beijing People's Republic of ChinaDepartment of Oncology, Beijing Friendship Hospital Capital Medical University Beijing People's Republic of ChinaDepartment of Oncology, Beijing Friendship Hospital Capital Medical University Beijing People's Republic of ChinaAbstract 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.https://doi.org/10.1002/cam4.70143gut microbiotaimmune‐checkpoint inhibitorinosinePD‐1/PD‐L1tumor |
| spellingShingle | Haiqing Zhao Wei Zhang Yuting Lu Yin Dong Zhihao He Hongchao Zhen Qin Li Inosine enhances the efficacy of immune‐checkpoint inhibitors in advanced solid tumors: A randomized, controlled, Phase 2 study Cancer Medicine gut microbiota immune‐checkpoint inhibitor inosine PD‐1/PD‐L1 tumor |
| title | Inosine enhances the efficacy of immune‐checkpoint inhibitors in advanced solid tumors: A randomized, controlled, Phase 2 study |
| title_full | Inosine enhances the efficacy of immune‐checkpoint inhibitors in advanced solid tumors: A randomized, controlled, Phase 2 study |
| title_fullStr | Inosine enhances the efficacy of immune‐checkpoint inhibitors in advanced solid tumors: A randomized, controlled, Phase 2 study |
| title_full_unstemmed | Inosine enhances the efficacy of immune‐checkpoint inhibitors in advanced solid tumors: A randomized, controlled, Phase 2 study |
| title_short | Inosine enhances the efficacy of immune‐checkpoint inhibitors in advanced solid tumors: A randomized, controlled, Phase 2 study |
| title_sort | inosine enhances the efficacy of immune checkpoint inhibitors in advanced solid tumors a randomized controlled phase 2 study |
| topic | gut microbiota immune‐checkpoint inhibitor inosine PD‐1/PD‐L1 tumor |
| url | https://doi.org/10.1002/cam4.70143 |
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