How do PARP inhibitors compare to docetaxel in the second line for mCRPC? In TRITON3, men with mCRPC progressing after treatment with ADT and a 2nd generation androgen receptor pathway inhibitor (ARPI) were screened for BRCA1, BRCA2, or ATM mutation. Of 4855 screened patients, 405 were randomized to treatment with either the PARP inhibitor rucaparib or physician’s choice of docetaxel or a different ARPI. Just over half of patients (~55%) received docetaxel. Most patients (75%) had BRCA mutations. The primary endpoint of median duration of radiographic progression free survival was significantly longer with rucaparib than physician’s choice (10.2 v 6.4 months). However, this improvement was mainly driven by those with BRCA mutations where median rPFS went from 6.4 to 11.2 months. In contrast, there was no improvement in median rPFS among the subset of patients with ATM mutations (8.1 v 6.8 months). Olaparib is also approved in this setting, however the PROfound trial didn’t include docetaxel as a treatment option as was done in TRITON3. So, TRITON3 supports the use of rucaparib in lieu of chemotherapy for BRCA mutated patients. | Fizazi, N Engl J Med 2023
