Alterations in homologous recombination repair (HRR) genes occur in 20%-30% of men with metastatic castration-resistant prostate cancer (mCRPC) which may increase sensitivity to platinum chemotherapy. Specifically, exceptional responses to platinum chemotherapy have been reported among patients with BRCA mutations. This study aimed to evaluate the efficacy of platinum chemotherapy in patients with mCRPC with and without HRR.
In this retrospective, multi-institution series, we analyzed patients with mCRPC to assess response to platinum-containing chemotherapy based on HRR alteration status. Outcome measures were prostate specific antigen (PSA)50 response rate (percentage of patients achieving at least a 50% decline in PSA from baseline), overall survival (OS) and progression-free survival (PFS).
From 1999 to 2020, 24 patients with mCRPC who received platinum chemotherapy were included with 7 patients analyzable for PSA outcomes. HRR alterations were found in 19 out of 24 patients (79.2%) with mutations recognized in 11 different HRR genes. Patients with a HRR alteration achieved a PSA50 response rate of 20% (1 out of 5) after platinum chemotherapy compared to 50% (1 out of 2) in patients without a HRR mutation. No difference in OS or PSA PFS was detected among patients with BRCA1/2 mutations compared to HRR alterations other than BRCA1/2 and patients without HRR alterations.
In patients with mCRPC, we did not find a statistical difference in anti-tumor activity after receiving platinum chemotherapy among patients harboring a pathogenic HRR alterations compared to patients without a HRR alteration. Additionally, we were unable to detect an association between BRCA1/2 mutation status and response to platinum chemotherapy. Platinum chemotherapy, however, had clinically meaningful activity in a subset of patients regardless of HRR alteration status. Additional studies are warranted using genomic data to predict sensitivity to platinum chemotherapy.
Clinical genitourinary cancer. 2024 Dec 12 [Epub ahead of print]
Stephanie Lakritz, Andrew Nicklawsky, Vida Alami, Manish Kohli, Chris Moskaluk, Greg Riedlinger, Bodour Salhia, Eric A Singer, Abdul Rafeh Naqash, Ken Nepple, Stephen Edge, Zin Myint, Jill Kolesar, Nabil Adra, Thomas Flaig, Laura S Graham
University of Colorado Cancer Center, Aurora, CO. Electronic address: ., University of Colorado Cancer Center, Aurora, CO., University of Utah Huntsman Cancer Institute, Salt Lake City, UT., University of Virginial Medical Center, Charlottesville, VA., Rutgers Cancer Institute of New Jersey, New Brunswick, NJ., Univeristy of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA., Ohio State University Wexner Medical Center, Columbus, OH., University of Oklahoma Health Sciences Center, Oklahoma City, OK., University of Iowa Holden Comprehensive Cancer Center, Iowa City, IA., Roswell Park Comprehensive Cancer Center, Buffalo, NY., University of Kentucky Markey Cancer Center, Lexington, KY., Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN.