PROfound
The first biomarker-selected trial in prostate cancer to improve survival, using a PARP inhibitor in men with BRCA-type mutations.
387 men (cohort A: BRCA1/2, ATM); rPFS 7.4 vs 3.6 months (HR 0.34); OS HR 0.69 despite crossover. Approval May 2020 for HRR-mutant mCRPC.
Setting
mCRPC with HRR gene alterations after ARPI: olaparib vs enzalutamide/abiraterone switch
Phase
Phase 3
Sponsor
AstraZeneca / Merck
Registry
Headline result
rPFS HR 0.34; OS HR 0.69 (cohort A).
Reported
2020
Enrolled
387
Replication
Consistent with TRITON3 (rucaparib in BRCA-altered mCRPC).
In plain words
What these results mean for people, not percentages
Radiographic progression-free survival, cohort A (BRCA1/2, ATM)primarysurrogate endpoint
- Median 7.4 vs 3.6 months with Olaparib compared with Enzalutamide or abiraterone; about 3.8 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 66 percent lower chance of the event at any given time (hazard ratio 0.34, likely range 0.25 to 0.47).
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
Overall survival, cohort Asurvival endpoint
- Median 19.1 vs 14.7 months with Olaparib compared with Enzalutamide or abiraterone; about 4.4 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 31 percent lower chance of the event at any given time (hazard ratio 0.69, likely range 0.5 to 0.97).
- Overall survival counts deaths from any cause, so it is the most direct measure of whether a treatment helps people live longer.
Be careful
- These results apply to the people the trial enrolled: mCRPC with HRR gene alterations after ARPI: olaparib vs enzalutamide/abiraterone switch. People in a different situation may not see the same effect.
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.
387 participants enrolled.
Radiographic progression-free survival, cohort A (BRCA1/2, ATM)primary
HR 0.34 (0.25–0.47) · p <0.001
Olaparib
7.4 mo
Enzalutamide or abiraterone
3.6 mo
Overall survival, cohort A
HR 0.69 (0.5–0.97) · p = 0.02
Olaparib
19.1 mo
Enzalutamide or abiraterone
14.7 mo
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Radiographic progression-free survival, cohort A (BRCA1/2, ATM)primary | Olaparib | 162 | 7.4 months | 0.34 (0.25–0.47) | <0.001 | link |
| Enzalutamide or abiraterone | 83 | 3.6 months | ||||
| Overall survival, cohort A | Olaparib | — | 19.1 months | 0.69 (0.5–0.97) | 0.02 | link |
| Enzalutamide or abiraterone | — | 14.7 months |
Replication
Consistent with TRITON3 (rucaparib in BRCA-altered mCRPC).