Loading
The first biomarker-selected trial in prostate cancer to improve survival, using a PARP inhibitor in men with BRCA-type mutations.
PROfound, trial NCT02987543 sponsored by AstraZeneca and Merck and reported in 2020, was the first biomarker-selected trial in prostate cancer to improve survival, using the PARP inhibitor olaparib in men with BRCA1, BRCA2 or ATM alterations. It randomised 387 men with metastatic castration-resistant prostate cancer and homologous recombination repair alterations after an androgen receptor pathway inhibitor to olaparib or a switch to enzalutamide or abiraterone, met its primary radiographic progression-free survival endpoint in cohort A with a large effect, and showed a survival benefit despite crossover, leading to approval in May 2020. OnCo links it to BRCA1 and BRCA2 and PARP as targets, to Maha Hussain and Johann de Bono. Whether ATM and other non-BRCA alterations truly benefit is the open question the cohort structure left behind.
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 enrolled.
| 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 to 0.47) | <0.001 | link |
| Enzalutamide or abiraterone | 83 | 3.6 months | ||||
| Overall survival, cohort A | Olaparib | - | 19.1 months | 0.69 (0.5 to 0.97) | 0.02 | link |
| Enzalutamide or abiraterone | - | 14.7 months |
Shares PROpel, TRITON3, Who is eligible for a PARP inhibitor in prostate cancer, and why the gene matters, Prostate cancer drugs in England: what NICE recommends, and what it refuses.
Shares PROpel, TRITON3, Who is eligible for a PARP inhibitor in prostate cancer, and why the gene matters, Prostate cancer drugs in England: what NICE recommends, and what it refuses.
Shares PARP, Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall, PARP inhibitors, Olaparib.
Shares PARP inhibitors, Olaparib, Metastatic castration-resistant prostate cancer, AstraZeneca.
Shares PARP inhibitors, Olaparib, Metastatic castration-resistant prostate cancer, AstraZeneca.
Shares PROfound: olaparib for metastatic castration-resistant prostate cancer with homologous recombination repair gene alterations, Johann de Bono, Olaparib, BRCA1 / BRCA2 (HRD).
Shares PARP, PARP inhibitors, Olaparib, BRCA1 / BRCA2 (HRD).
Shares PARP, PARP inhibitors, Olaparib, BRCA1 / BRCA2 (HRD).