Efficacy
A summary of the efficacy can be seen in the table below.
Study |
Total no. of patients (pts) |
Treatment arm |
Control arm |
Event-free survival at 12 months |
Median survival |
Hazard ratio for death |
Response Rate (CR/CRh) |
Montesinos et al. 2022 (AGILE study)r |
146 pts |
72 pts ivosidenib-and-azacitidine (IVO+AZA) |
74 pts placebo-and-azacitidine (PBO+AZA) |
34% vs 12% |
24 vs 7.9 months |
0.44; 95% CI, 0.27 to 0.73; P=0.001 |
53% vs 18% |
The primary endpoint for the study was event-free survival (EFS). With a median follow-up time of 12.4 months, EFS was significantly longer in the IVO+AZA group vs PBO+AZA group (hazard ratio [HR] for treatment failure, relapse from remission, or death, 0.33; 95% confidence interval [CI], 0.16 to 0.69; P=0.002). Because more than half the patients in each group did not have complete remission (CR) by week 24, the median EFS was the same in the two groups (0.03 months [95% CI, 0.03 to 11.01]). The estimated probability a patient would remain event-free was 40% at 6 months and 37% at 12 months in the IVO+AZA group, as compared with 20% at 6 months and 12% at 12 months in the PBO+AZA group. The median overall survival (mOS) with IVO+AZA was 24.0 months (95% CI, 11.3 to 34.1) and 7.9 months (95% CI, 4.1 to 11.3) with PBO+AZA (HR for death, 0.44; 95% CI, 0.27 to 0.73; P=0.001)(Figure 1).r
Figure 1. Survival analysis at the time of initial study closurer

©The New England Journal of Medicine 2022
A longer term follow-up analysis has been conducted with a median follow-up time of 28.6 months. This showed the mOS to be 29.3 months (95% CI: 13.2 to not reached) for IVO+AZA versus 7.9 months (95% Cl, 4.1 to 11.3) for PBO+AZA (HR 0.42 [95% CI, 0.27 to 0.65]; 1-sided p<0.0001) (Figure 2).r
Figure 2. Longer-term survival analysis after study unblindingr

©American Society of Clinical Oncology 2023
Complete remission was 47% (95% CI, 35 to 59) in the IVO+AZA group and 15% (95% CI, 8 to 25) in the PBO+AZA group (P<0.001). The median duration of CR was not reached with IVO+AZA and was 11.2 months (95% CI, 3.2 to could not be estimated) with PBO+AZA. The median time to CR was 4.3 months (range, 1.7 to 9.2) with IVO+AZA and 3.8 months (range, 1.9 to 8.5) with PBO+AZA and CR or CRh occurred in 53% (95% CI, 41 to 65) and 18% (95% CI, 10 to 28) of patients, respectively (P<0.001). The median duration of treatment was 6.0 months (range, 0.1 to 33.5) with ivosidenib and azacitidine and 2.8 months (range, 0.1 to 19.8) with placebo and azacitidine.r
Table 1. Haematologic response, response duration and time to response (intention-to-treat population)r

©The New England Journal of Medicine 2022
After an initial decline in both groups consistent with the time to response, health-related quality of life with ivosidenib and azacitidine was similar to or improved from baseline for most subscales from cycle 5 through cycle 19 when a 10-point threshold for clinically meaningful change was applied. Improvements from baseline did not occur for any subscale with placebo and azacitidine.r
Although no interim analysis was planned according to the protocol, the statistics and data management centre noted a difference in the number of deaths favouring ivosidenib and azacitidine and the trial recruitment was discontinued on May 27, 2021, almost 4 years after its commencement in June 2017.r