RATIFY (CALGB 10603)
The trial that made FLT3 the first targetable mutation in AML: adding midostaurin to chemotherapy tripled median survival.
3,277 patients screened to randomise 717 with FLT3-ITD or TKD mutations. Median OS 74.7 vs 25.6 months (HR 0.78, 95% CI 0.63-0.96, p=0.009); 4-year OS 51.4% vs 44.3%; benefit across ITD allelic ratio and TKD subgroups and irrespective of transplant. NEJM 2017. Established the template of TKI added to intensive induction that QuANTUM-First later refined.
Setting
Newly diagnosed FLT3-mutated AML, age 18-59: midostaurin vs placebo added to 7+3, consolidation, and one year of maintenance
Phase
Phase 3
Sponsor
Alliance / Novartis
Registry
Headline result
Median OS 74.7 vs 25.6 months; HR 0.78.
Reported
2017
Enrolled
717
Replication
QuANTUM-First (quizartinib) independently confirmed that FLT3 inhibition added to 7+3 improves OS in FLT3-ITD AML; real-world registries reproduce the RATIFY benefit in patients up to age 70.
In plain words
What these results mean for people, not percentages
Overall survival (median)primarysurvival endpoint
- Median 74.7 vs 25.6 months with Midostaurin + 7+3 compared with Placebo + 7+3; about 49.1 months longer for half the group.
- A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
- Put another way, the treated group had about 22 percent lower chance of the event at any given time (hazard ratio 0.78, likely range 0.63 to 0.96).
4-year overall survivalsurvival endpoint
- 51.4 vs 44.3 out of 100 alive at 4 years with Midostaurin compared with Placebo; 7.1 more per 100.
- Roughly one extra person helped for every 14 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
Be careful
- Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
- These results apply to the people the trial enrolled: Newly diagnosed FLT3-mutated AML, age 18-59: midostaurin vs placebo added to 7+3, consolidation, and one year of maintenance. People in a different situation may not see the same effect.
- The trial selected people by a biomarker (FLT3); the result should not be assumed for people whose cancer does not have it.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
717 participants enrolled.
Overall survival (median)primary
HR 0.78 (0.63–0.96) · p = 0.009
Midostaurin + 7+3
74.7 mo
Placebo + 7+3
25.6 mo
4-year overall survival
Midostaurin51.4 of 100
Placebo44.3 of 100
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Overall survival (median)primary | Midostaurin + 7+3 | 360 | 74.7 months | 0.78 (0.63–0.96) | 0.009 | link |
| Placebo + 7+3 | 357 | 25.6 months | ||||
| 4-year overall survival | Midostaurin | — | 51.4% | — | — | — |
| Placebo | — | 44.3% |
Replication
QuANTUM-First (quizartinib) independently confirmed that FLT3 inhibition added to 7+3 improves OS in FLT3-ITD AML; real-world registries reproduce the RATIFY benefit in patients up to age 70.