Prevalence and clinical impact of BRCA1/2 mutations in patients with de novo metastatic hormone-sensitive prostate cancer (mHSPC).

Authors

null

Nieves Martinez Chanza

Jules Bordet Institute, Brussels, Belgium

Nieves Martinez Chanza , Marie Tkint De Roodenbeke , Laurence Desmyter , Francoise Wilkin , Cindy Badoer , Isabelle Vandernoot , Guillaume Smits , Anna Ayako Accarain , Spyridon Sideris , Thierry Gil , Ahmad Awada , Thierry Andre Roumeguere , Anis Hamid

Organizations

Jules Bordet Institute, Brussels, Belgium, Jules Bordet Institute, Brussel, Belgium, Erasme Hospital, Brussels, Belgium, Institut Jules Bordet, Bruxelles, Belgium, Institut Jules Bordet, Brussels, Belgium, Erasme Hospital, University Clinics of Brussels, Brussels, Belgium, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA

Research Funding

No funding received
None.

Background: Somatic BRCA gene mutations (sBRCAm) have been identified in a significant proportion of patients (pts) with castration resistant PC (CRPC), with mixed data regarding effect on CRPC therapies. However, the prevalence and clinical significance in mHSPC are not well characterized. Methods: Sequencing of primary tumor for sBRCA1/2 was performed in unselected pts with de novo mHSPC. We assessed the association of sBRCAm on time to CRPC (TTCRPC) and overall survival (OS) from diagnosis using Kaplan-Meier method, as well as PSA response (50% fall from baseline). Associations were evaluated using a Cox regression model with multivariable analyses adjusting for docetaxel use. Results: We identified 69 pts with de novo mHSPC, of whom 7 (10%) harbored a pathogenic sBRCA2m. Median age at diagnosis was 66 years. The majority were classified as high volume disease (n=54; 84%) with Gleason 9-10 grade (n=40; 61%). Therapies in the HSPC setting included ADT alone (n=29, 42%), ADT + Docetaxel (n=35, 51%), and ADT + Docetaxel + Abiraterone (n=5, 7%). Only 1 sBRCA2m case compared to 39 wild-type pts were treated with docetaxel. PSA response was achieved in 65 (96%) and PSA £ 0.2 ng/ml at 7 mos in 20 (31%) pts, without significant association with BRCA status (p=0.13 and p=0.66, respectively). At a median FU of 29 mos, CRPC occurred in 44 (64%) pts with a median TTCRPC of 24 mos. TTCRP was numerically shorter for non-mutated pts compared to sBRCAm (22 vs. 40 mos, HR 0.5, p=0.23); there was no significant association with docetaxel use. In multivariate analyses, there was no significant association between sBRCAm and TTCRPC (HR 0.43, p=0.175). Median OS was 74 mos without any difference according to BRCA status (p=0.30) nor docetaxel use (p=0.14). Conclusions: In this real-world study of routine sBRCA1/2 assessment, we found a 10% prevalence in de novo mHSPC. Time to CRPC trended longer in the sBRCAm population despite less use of docetaxel, indicating that pts with sBRCAm appear to have at least similar outcomes with standard mHSPC therapies. Larger datasets correlating genomics with outcomes in this subset of pts are warranted.

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Abstract Details

Meeting

2020 Genitourinary Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session A: Prostate Cancer

Track

Prostate Cancer - Advanced,Prostate Cancer - Localized

Sub Track

Patient-Reported Outcomes and Real-World Evidence

Citation

J Clin Oncol 38, 2020 (suppl 6; abstr 44)

Abstract #

44

Poster Bd #

B10

Abstract Disclosures