DURHAM, NC — While the effects of BRCA2 mutation are well known related to breast cancer risk in women, men also face heightened risk of cancer, including prostate cancer.
A 2019 study pointed out that, after three years of screening, BRCA2 mutation carriers had a higher incidence of prostate cancer, younger age of diagnosis, and more clinically significant tumors, compared to noncarriers.1
That is why so much current focus is on which therapies work well in carriers of the BRCA2 germline mutation. Research at the 2021 American Society of Clinical Oncology (ASCO) annual meeting noted that PARP inhibitors (PARPis) were approved by the U.S. Food and Drug Administration for the treatment of advanced prostate cancer (PC) among patients harboring mutations in genes responsible for homologous DNA repair.2
Authors from the Duke University School of Medicine, the Durham, NC, VA Healthcare System and the Cleveland Clinic Foundation pointed to increasing evidence that patients with BRCA2 gene alterations might accrue the most benefit from that therapy.
The researchers sought to evaluate real-world treatment outcomes among veterans prescribed PARPis for PC and to compare outcomes between patients with BRCA2 gene variants and those with variants in other homologous DNA repair genes.
To do that, they reviewed the VA’s National Precision Oncology Program database to identify PC patients who successfully underwent tumor DNA sequencing and were prescribed olaparib, rucaparib, niraparib or talazaporib prior to FDA approval for PARPi use in PC, which occurred on May 15, 2020.
Included in outcomes assessments were 43 patients who received a PARPi for more than four weeks. The VA’s Corporate Data Warehouse was reviewed to obtain clinical and disease characteristics, laboratory and imaging reports, and treatments administered.
Specifically, the study team assessed PSA30, defined as the percentage of patients achieving a 30% reduction in prostate-specific antigen (PSA) level, and composite progression-free survival (PFS), which included time to radiographic progression per RECIST criteria, discontinuation of therapy, and/or death. Analysis did not include patients who discontinued therapy because of toxicity.
The most commonly observed gene variant was BRCA2, affecting 43.8%, followed by ATM (23.0%) and BRCA1 (16.7%). Most, 87.5%, of patients received prior systemic therapy beyond androgen deprivation. The largest group of patients, 83.3%, were treated with olaparib, followed by rucaparib, 12.5%; two (4.2%) received both. The authors advised that 11 patients discontinued therapy due to toxicity, most commonly anemia.
Using t-testing and log-rank testing, respectively, researchers compared PSA30 and PFS between patients with BRCA2 gene variants and those with variants in other homologous DNA repair genes.
Results indicated that, of the 43 patients treated for more than four weeks, BRCA2 variants had a higher rate of PSA30 than those without — 47.9% vs. 4.5%. With median progression-free survival for all patients at four months, those with BRCA2 gene variants had longer PFS than those without BRCA2 gene variants –7.2 vs 3.3 months — and also had longer PFS than those with BRCA1 variants — 7.2 vs 3.3. No difference was observed in PFS between those with BRCA2 variants and those with ATM variants, however.
“Approximately one-quarter of PC patients with variants in homologous DNA repair genes treated with PARPis achieve a 30% reduction in PSA, and the median PFS is 4 months,” researchers concluded. “Patients harboring BRCA2 gene variants have a significantly higher rate of PSA30 and a longer PFS than those with variants in other homologous DNA repair genes.”
- Page EC, Bancroft EK, Brook MN, Assel M, et. Al. Hassan Al Battat M, Thomas S, Taylor N, Chamberlain A, Pope J, Raghallaigh HN, Evans DG, Interim Results from the IMPACT Study: Evidence for Prostate-specific Antigen Screening in BRCA2 Mutation Carriers. Eur Urol. 2019 Dec;76(6):831-842. doi: 10.1016/j.eururo.2019.08.019. Epub 2019 Sep 16. PMID: 31537406; PMCID: PMC6880781.
- Price M, Vashistha V, Winski D, Kelley M. (June 4-8, 2021) Real-world outcomes among prostate cancer patients with BRCA2 gene variants compared to variants in other homologous DNA repair genes. ASCO 2021 annual meeting. Virtual. https://meetinglibrary.asco.org/record/198412/abstract
