Neal D. Shore, MD, on Germline Genetic Testing and Its Impact on Prostate Cancer Clinical Decision-Making
2022 ASCO Annual Meeting
Neal D. Shore, MD, of the Carolina Urologic Research Center, discusses his study findings, showing that germline genetic testing influenced care for patients with prostate cancer. Men whose genetic test was positive for a pathogenic germline variant received more recommendations for changes to follow-up and treatment, and for testing and counseling of relatives, than did patients with negative or uncertain test results (Abstract 10500).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
1,000 patients, prospectively analyzed for pathogenic variations via germline testing. That's what we did, 15 US urology sites, combining both community and academic sites. We presented our findings at ASCO 2021. At that point we revealed, in an oral podium presentation, that 50% of the PGVs, the pathogenic variants of germline, were within NCCN criteria and 50% were outside NCCN criteria. At ASCO 2022, we're presenting now the clinical considerations. What did our colleagues do with this information? Again, of note, 50% of the patients who received germline testing, would've fallen outside of NCCN criteria. This is important because we're really trying to democratize, and open up, germline testing to anyone with a diagnosis of prostate cancer. In our study, it included patients who had metastatic disease, biochemical relapse, newly diagnosed, prostate cancer. Furthermore, of our 1000 patients, 21% identified as nonwhite, so we had a very significant Black and Latino population. I think this is incredibly important given the ongoing themes of inclusion, equity, and disparity, which ASCO is promoting. Of note of our patients, 10% had pathogenic variants. Interestingly, it was around a discordance of 12% white and 4% in the black population, despite the 80-20% prevalence that we obtained. Now, interestingly, we had a two thirds higher number of patients in the black population who had alterations, gene alterations, of uncertain variations, or VUSs. This, I think, speaks to the fact that we've normalized VUS in a much greater way for the white population, not just in the US, but globally. Regarding the clinical considerations, our colleagues utilized clinical trials when there were PGVs that were found positive. The top five PGVs of the five, four out of the five were in DDR alterations. As we all know, we have PARP inhibitors and other findings that are actionable, certainly in the US, there's an FDA approval for PARP inhibition. Then another significant amount of patients went on to clinical trials. Remarkably and profoundly, more than two thirds of patients ultimately received referral to certified genetic counselors, or some form of genetic counseling, via telehealth, or from the sites themselves. There are certain limitations to our study in that it was a one shot time assessment. We are looking at longitudinal assessments. These were in urology community practices. It may be different at academic medical oncology sites, but what's important to note is that this had a very favorable, when we looked at questionnaires from the sites that participated, that they felt us, it was not only implementable, actionable, but also of great value for them as well as in the patient physician shared decision making.
Bradley J. Monk, MD, of the University of Arizona College of Medicine and Creighton University School of Medicine, discusses phase III findings from the ATHENA–MONO (GOG-3020/ENGOT-ov45) trial. It showed that rucaparib as first-line maintenance treatment, following first-line platinum-based chemotherapy, improved progression-free survival in patients with ovarian cancer, irrespective of homologous recombination deficiency status (Abstract LBA5500).
Courtney D. DiNardo, MD, MSCE, of The University of Texas MD Anderson Cancer Center, and Stéphane de Botton, MD, PhD, of Institut Gustave Roussy, discuss phase III findings from the IDHENTIFY trial, which showed that mutational burden and co-mutational profiles differed between patients with relapsed or refractory acute myeloid leukemia that exhibited IDH2-R140 and IDH2-R172 mutations. Enasidenib improved survival outcomes for patients with IDH2-R172 mutations: median overall survival and 1-year survival rates were approximately double those in the conventional care arm (Abstract 7005).
Erika Hamilton, MD, of Sarah Cannon Research Institute at Tennessee Oncology, discusses phase III data from the DESTINY-Breast03 study, which reinforced the consistent safety profile of fam-trastuzumab deruxtecan-nxki (T-DXd) vs ado-trastuzumab emtansine (T-DM1) in patients with HER2-positive unresectable and/or metastatic breast cancer. The findings also support T-DXd’s risk benefit over that of T-DM1 (Abstract 1000).
Alicia K. Morgans, MD, MPH, of Dana-Farber Cancer Institute, and Ian D. Davis, PhD, MBBS, of Monash University and Eastern Health, discuss the latest findings from ANZUP Cancer Trials Group’s ENZAMET cooperative group trial of enzalutamide in patients with metastatic hormone-sensitive prostate cancer. The results corroborate the benefit of enzalutamide with improved overall survival, and involve some exploratory subgroup analyses (Abstract LBA5004).
Benoit You, MD, PhD, of Lyon University hospital (HCL, France) and GINECO group (France), discusses findings from the GOG-0218 trial of patients with ovarian cancer, which appears to confirm earlier data on the link between poor tumor chemosensitivity and benefit from concurrent plus maintenance bevacizumab. In Dr. You’s validation study, patients who derived the most progression-free and overall survival benefit from bevacizumab were those with high-risk disease (stage IV or incompletely resected stage III) associated with an unfavorable KELIM score (CA-125 kinetic elimination rate constant, calculable online) (Abstract 5553).