An interview with Dr. Nadine Tung and Dr. Dana Zakalik, co-chairs on ”Adjuvant PARP Inhibitors in Patients with High-risk Early-Stage HER2-Negative Breast Cancer and Germline BRCA Mutations: ASCO Hereditary Breast Cancer Guideline Rapid Recommendation Update.” They discuss the results and impact of the OlympiA trial, the updated recommendation, and outstanding questions on the use of PARP inhibitors in the adjuvant setting. For more information, visit www.asco.org/breast-cancer-guidelines.   TRANSCRIPT [MUSIC PLAYING] ANNOUNCER: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. BRITTANY HARVEY: Hello and welcome to the ASCO Guidelines Podcast Series, brought to you by the ASCO Podcast Network, a collection of nine programs covering a range of educational and scientific content, and offering enriching insight into the world of cancer care. You can find all the shows, including this one, at podcast.ASCO.org. My name is Brittany Harvey, and today I'm interviewing Dr. Nadine Tung from Beth Israel Deaconess Medical Center in Boston, Massachusetts, and Dr. Dana Zakalik from Beaumont Health in Royal Oak, Michigan, co-chairs of the Management of Hereditary Breast Cancer Guideline Expert Panel and this rapid recommendation update, Adjuvant PARP Inhibitors in Patients With High-Risk Early-Stage HER2-Negative Breast Cancer and Germline BRCA Mutations: ASCO Guideline Recommendation Update. Thank you for being here, Dr. Tung and Dr. Zakalik. DR. ZAKALIK: Thank you for having us. DR. TUNG: Thank you so much. Pleasure to be here. BRITTANY HARVEY: First, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The full conflict of interest information for this guideline panel is available online. Dr. Tung, do you have any relevant disclosures that are directly related to this guideline topic? DR. TUNG: I do receive research funding from AstraZeneca, as I run a trial using a PARP inhibitor in breast cancer. BRITTANY HARVEY: Thank you. And Dr. Zakalik, do you have any relevant disclosures? DR. ZAKALIK: I do not. BRITTANY HARVEY: Thank you. Then let's get into the meat of this rapid recommendation update. So, Dr. Tung, what prompted this rapid update to a recommendation from the Management of Hereditary Breast Cancer Guideline? DR. TUNG: The OlympiA Trial, which was presented at ASCO this past June and published the same day in the "New England Journal of Medicine." OlympiA was a large Phase III trial, which demonstrated that a year of adjuvant olaparib, a PARP inhibitor, significantly improved both invasive disease-free survival by nearly 9%, and distant disease-free survival by a similar improvement, in germline BRCA mutation carriers with HER2-negative breast cancer and a high risk of recurrence. Overall survival was numerically better with olaparib, but it didn't yet reach significant improvement as a stringent p-value was required for this early reporting. And I say early reporting because the trial was reported early after the first event-driven interim analysis showed a benefit with olaparib. 1,800 patients had been enrolled with a median follow up of 2 and 1/2 years at the reporting. But the follow up was 3 and 1/2 years for the first 900 patients enrolled, known as the maturity cohort. And it was comforting that the significant improvement in invasive disease-free survival and distant disease-free survival was also seen when just looking at that maturity cohort. So for those who might think that it's too early and that these benefits might not hold up with longer follow up, it's very comf