“A few months ago, olaparib (Lynparza, AstraZeneca) was the first drug approved to treat women with advanced breast cancer with germline mutations in BRCA.
“That approval was based on a significant improvement in progression-free survival (PFS) compared with standard chemotherapy shown in the OlympiAD trial. The results led to quite some excitement among breast cancer researchers, as for example in the Medscape Oncologycommentary ‘OlympiAD: Olaparib Captures Gold for BRCA-Mutated Breast Cancer Patients.’
“Now, however, a final analysis of OlympiAD results shows that overall survival (OS) did not significantly improve.”
“Improvements in progression-free survival (PFS) with olaparib (Lynparza) over treatment of physician’s choice (TPC) remained consistent regardless of baseline tumor burden for patients with HER2-negative breast cancer with a germline BRCA1/2 mutation (gBRCA1/2m), according to an exploratory analysis from the phase III OlympiAD trial presented at the 2018 Miami Breast Cancer Conference (MBCC).
“Although not powered to show statistical significance between the groups, in those with one metastatic site (n = 71) the median PFS with olaparib was 8.4 months compared with 4.2 months with TPC (HR, 0.62; 95% CI, 0.35-1.13). In patients with ≥2 metastatic sites (n = 231), the median PFS was 6.5 months with olaparib compared with 3.0 months for TPC, which crossed the barrier for statistical significance (HR, 0.59; 95% CI, 0.43-0.82).”
“The FDA authorized marketing the direct-to-consumer Personal Genome Service Genetic Health Risk Report for three mutations of BRCA1 and BRCA2 most common among people of Eastern European Ashkenazi Jewish descent, according to a press release.
“The test — marketed by 23andMe — analyzes DNA using self-collected saliva samples to determine whether a woman is at increased risk for breast and ovarian cancer and whether a man is at increased risk for breast or prostate cancer.”
“The PARP inhibitor talazoparib significantly increased progression-free survival (PFS) over physician’s choice of therapy in a randomized phase III trial of patients with advanced breast cancer and a germline BRCA mutation.
“ ‘Talazoparib is a highly potent, dual-mechanism PARP inhibitor. It prevents the repair of DNA damage, and results in cell death,’ said Jennifer K. Litton, MD, of the University of Texas MD Anderson Cancer Center in Houston. A previous phase II study showed encouraging efficacy with the agent in patients with BRCA1/2 mutations, which led to the new EMBRACA trial. Litton presented results of the trial at the 2017 San Antonio Breast Cancer Symposium (SABCS), held December 5–9.”
“Of the women who carry the mutated BRCA1/2 genes, 45-65 percent will develop breast cancer, and 15-39 percent will develop ovarian cancer in their lifetimes. Many women, especially those who have experienced the death of family members to these cancers, elect to undergo preventive surgeries that can significantly increase life expectancy, but require extensive recovery time and can impact later fertility and quality-of-life. However, few guidelines exist that shed light on the optimal age to undergo these procedures, and in what sequence. A new study in the INFORMS journal Decision Analysis provides insight to help enable physicians and patients make better-informed choices.
“The study, ‘Was Angelina Jolie Right? Optimizing Cancer Prevention Strategies Among BRCA Mutation Carriers,’ was conducted by Eike Nohdurft and Stefan Spinler of the Otto Beisheim School of Management, and Elisa Long, of the UCLA Anderson School of Management.”
“Two new studies presented at the Annual Scientific Meeting of the American Urological Association (AUA) offer an improved understanding of some genetic underpinnings of prostate cancer. In one, researchers found that BRCA mutations may raise the risk of the malignancy substantially, while another found a high rate of mutations among other DNA repair genes as well.
” ‘These studies reveal new insights into the role genetic mutations play in the development of prostate cancer, particularly metastatic disease,’ said Scott Eggener, MD, of the University of Chicago Medicine, who moderated the session with these studies, in a press release.”
“AstraZeneca today announced positive results from its Phase III OLYMPIAD trial comparing Lynparza (olaparib) tablets (300mg twice daily) to physician’s choice of a standard of care chemotherapy in the treatment of patients with HER2-negative metastatic breast cancerharbouring germline BRCA1 or BRCA2 mutations. Patients treated with Lynparza showed a statistically-significant and clinically-meaningful improvement in progression-free survival (PFS) compared with those who received chemotherapy (capecitabine, vinorelbine or eribulin).”
“Clinical data on the role of platinum salts in the treatment of triple-negative breast cancer (TNBC) — particularly germline (g) BRCA1-related TNBC — are encouraging in the neoadjuvant setting, where the pathologic complete response rate is improved with the addition of a platinum to anthracycline and taxane-based chemotherapy.
“Data have emerged to show the utility of incorporating platinums into the metastatic setting in TNBC as well, with the strongest evidence for use in patients who are BRCA1/2 mutation carriers or who express a BRCA-like genomic instability signature.”
“Joanne Blum, MD, PhD, breast medical oncologist, director, Hereditary Cancer Risk Program, Baylor Charles A. Sammons Cancer Center, discusses the function of the oral PARP inhibitor talazoparib (BMN 673) in BRCA mutation subjects with locally advanced and/or metastatic breast cancer. Blum says the BRCA mutation works in combination with talazoparib in order to better cut off the appropriate pathways for the tumors.
“Blum said during the phase I trial that looked at talazoparib, patients experienced grade 1 neutropenia, cytopenia and fatigue. Blum added that the toxicities were very mild.”