FDA defined HRD genes critical for response to PARPi in prostate cancer
Piotr J. Wysocki
MD, PhD, medical oncologist; Professor of Medicine, Head of Department of Oncology, Jagiellonian University Hospital. ASCO International Affairs Committee member
A pooled patient-level data from trials of PARPi in mCRPC revealed 4 critical HRD genes whose impairment was associated with the benefit of PARP inhibition.
BRCA1m (N = 64), rPFS HR was 0.51 (0.23 to 1.1) and OS HR was 0.74 (0.34 to 1.61)
BRCA2m (N = 422), rPFS HR was 0.31 (0.23 to 0.42) and OS HR was 0.66 (0.49 to 0.89)
CDK12m (N = 164), rPFS HR was 0.50 (0.32 to 0.80) and OS HR was 0.63 (0.39 to 0.99)
PALB2m (N = 41) rPFS HR was 0.52 (0.23 to 1.17) and OS HR was 0.78 (0.34 to 1.8)
Surprisingly mutations in ATM and CHECK2 were not shown to correlate with the benefit of PARPi
ATMm (N = 268), rPFS HR was 1.05 (0.74 to 1.49) and OS HR was 1.18 (0.82 to 1.71)
CHEK2m (N = 172), rPFS HR was 1.06 (0.67 to 1.66) and OS HR was 1.53 (0.95 to 2.46)