Findings from a systematic literature review further our understanding of the prevalence of distinct clinical states of advanced prostate cancer, their association with homologous recombination repair (HRR) gene alterations, and the use of testing methods to identify HRR gene alterations, researchers say.
Findings from a systematic literature review further our understanding of the prevalence of distinct clinical states of advanced prostate cancer, their association with homologous recombination repair (HRR) gene alterations, and the use of testing methods to identify HRR gene alterations, researchers say. The data provide important background for appropriate patient care decision making.
They are particularly noteworthy given the anticipated shift in the treatment landscape that is ushering in a new era of personalized medicine, said Neal Shore, MD, at the 2020 Genitourinary Cancers Symposium in San Francisco.
The study involved searches of 9 databases for relevant English-language articles published from January 2009 to May 2019 and of conference proceedings from 10 meetings held from 2014 to 2019. Investigators identified more than 4700 papers that were systematically screened, of which 24 met inclusion criteria and underwent detailed review.
Among the main findings, data showed global increases in the incidence and prevalence of meta-static hormone-sensitive prostate cancer (mHSPC), nonmetastatic castrate-resistant prostate cancer (nmCRPC), and metastatic CRPC (mCRPC), a relatively high prevalence of HRR gene alter-ations in prostate cancer, and substantial variation in HRR gene testing. “This comprehensive, detailed review and meta-analysis of a decade of reports identified in global databases has provided numerous interesting findings, notwithstanding the caveats of a retrospective analysis and the associated challenges that variability in reporting and defini-tions created for quantifying and synthesizing the information,” said Shore, medical director at the Carolina Urologic Research Center in Myrtle Beach, South Carolina.
“Understanding current real-world evidence regarding the epidemiology of and practice trends for mHSPC, nmCRPC, and mCRPC and HRR gene alterations is important as we look forward to the availability of therapies, specifically poly [ADP ribose] polymerase [PARP] inhibitors, that have shown benefit for men with mCRPC harboring certain HRR gene alterations, and the spate of clinical trials investigating these drugs in all stages of metastatic PC.”
According to the meta-analysis, approximately 20% of men with mCRPC and 10% to 15% of men with mHSPC have HRR gene alterations, suggesting they could potentially benefit from PARP inhibitor treatment. Of the studies that were reviewed for information on HRR gene alterations, most focused on germline testing. Therefore, limit-ed data were captured on the prevalence of somatic HRR alterations.
“Germline testing, which is done to identify inherited genetic alterations, can be done using a blood or saliva sample. A tumor sample is required now to test for somatic HRR gene alterations that arise de novo in the prostate cancer, but liquid [blood-based] testing for somatic alterations is also forthcoming,” Shore explained.
“The need to test for somatic HRR gene alterations in men who have a negative result by germ-line testing is highlighted by analyses that doing both types of tests may double the proportion of patients found to have an actionable HRR gene alteration.”
The National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology for prostate cancer recommend performing germline genetic testing in men with prostate cancer with a positive family history as well as in those with high-risk, very high-risk, regional, or metastatic prostate cancer, Ashkenazi Jewish ancestry, or intraductal histology. The guidelines state that somatic tumor testing for HRR gene mutations can be considered in patients with regional or metastatic prostate cancer.
“In addition to providing information that can be relevant for precision care and counseling for some prostate cancer patients, the finding of certain HRR germline mutations has implications for cascade family testing in order to identify cancer risk genes for family members who may be at risk for ovarian, breast, colorectal, and other cancers,” Shore said.
Disclosure: Merck provided funding for the study. Shore does research/consulting for Merck, AstraZeneca, Clovis Oncology, Myriad, and Invitae. For full disclosures, see bit.ly/229disclosures.