Outcomes of patients with metastatic castration resistant prostate cancer according to somatic sequencing of domage DNA repair genes.

Abstract

e17595 Background: More than 20% of mCRPC present somatic DNA damage repair gene mutation (DDR). If some data are available for germline mutations, there are few studies describing the relation between somatic alterations and response to standard therapies in mCRPC. Methods: To describe outcomes of mCRPC patients treated with standard therapies according to somatic DDR status.A retrospective somatic analysis on a 69-gene panel was conducted among mCRPC patients. Progression-free survival (PFS) of first-line treatment was analyzed according to somatic DDR mutation as primary endpoint. First exposition to taxanes chemotherapy and PFS2 (time to the second event of disease progression) depending on therapeutic sequences (new-generation hormonotherapy [NGHT]/taxanes chemotherapy) were also analyzed. Results: Among 83 patients tested, 33 (40%) had a somatic DDR mutation, including 10 ATM, 5 BRCA2, 4 CHEK2, 3 CDK12, 3 FANCG, 1 BLM, 1 CHEK1, 1 FANCF, 1 FANCI, 1 FANCM, 1 MDC1, 1 MRE11A and 1 PALB2. In first-line treatment, 20 patients received taxanes and 63 NGHT. Median PFS was 9.8 months for mutated patients and 8.4 months for non-mutated patients (p = 0.9). For mutated patients, median PFS was 12.3 months in taxanes group and 9.8 months in NGHT group, (p = 0.74). One BRCA2-mutated patient treated by docetaxel was particularly long responder (PFS = 39.2 months). PFS of first exposition to taxanes was 8.2 months among mutated patients and 5.7 months among non-mutated patients (p = 0.31). Patients with BRCA1/BRCA2/ATM mutations had longer PFS compared to the others patients (10.6 months versus 5.5 months, p = 0.04). Ten patients received the chemotherapy-NGHT sequence (CHS) and 28 the NGHT-chemotherapy sequence (HCS). PFS2 were 16.5 months for mutated patients, whatever the sequence, and 11.7 months among non-mutated patients (p = 0.07). The 3 mutated patients (1 BRCA1, 1 BRCA2, 1 ATM mutation) had long PFS2 in the CHS (49.8 months). PFS2 of mutated patients in HCS was 15.6 months. Conclusions: Mutated mCRPC patients benefit from standard therapies, with long responders to taxanes among patients with BRCA1/2 and ATM mutations.