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.
The ASCO Post Staff
Tara B. Sanft, MD, of Yale University, discusses the results of the LEANer study (Lifestyle, Exercise, and Nutrition Early After Diagnosis) in women with breast cancer. It showed that patients with newly diagnosed disease who were just starting chemotherapy could improve physical activity and diet quality. While both groups had high rates of treatment completion, women in the intervention who exercised at or above the recommended levels did better in terms of treatment completion, with fewer dose reductions and delays (Abstract 12007).
The ASCO Post Staff
Georgina V. Long, MD, PhD, of the Melanoma Institute Australia, The University of Sydney, discusses phase III findings from the KEYNOTE-716 study. The trial showed that compared with placebo, adjuvant pembrolizumab significantly improved distant metastasis–free survival in patients with resected stage IIB and IIC melanoma. The findings also suggest a continued reduction in the risk of recurrence and a favorable benefit-risk profile (Abstract LBA9500).
Lisa A. Carey, MD, of the University of North Carolina Lineberger Comprehensive Cancer Center, and Hope S. Rugo, MD, of the University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, discuss phase III results from the TROPiCS-02 trial. This study showed that sacituzumab govitecan-hziy was more beneficial than single-agent chemotherapy in terms of progression-free survival in heavily pretreated patients with hormone receptor–positive/HER2-negative and unresectable advanced breast cancer (LBA1001).
The ASCO Post Staff
Mairéad G. McNamara, PhD, MBBCh, of The Christie NHS Foundation Trust, discusses phase II findings of the NET-02 trial, which explored an unmet need in the second-line treatment of patients with progressive, poorly differentiated extrapulmonary neuroendocrine carcinoma. In the trial, the combination of liposomal irinotecan, fluorouracil, and folinic acid, but not docetaxel, met the primary endpoint of 6-month progression-free survival rate (Abstract 4005).
The ASCO Post Staff
Pamela L. Kunz, MD, of the Yale University School of Medicine, discusses new findings from the ECOG-ACRIN E2211 trial, which showed the longest progression-free survival and highest response rates with temozolomide plus capecitabine reported to date for patients with pancreatic neuroendocrine tumors. The presence of a deficiency of MGMT, the drug-resistance gene, was associated with greater odds of an objective response (Abstract 4004).