The 55th annual ASCO (American Society of Clinical Oncology) meeting took place in Chicago May 31 through June 4, 2019. Over 30,000 oncology professionals attended, and thousands of abstracts were presented at the event, laying out the latest advances in diagnostic strategies and targeted therapies for pancreatic, breast, prostate and pediatric cancers, among others. One of the most anticipated presentations of ASCO 2019 illustrated the preliminary results of the phase-III clinical trial evaluating Olaparib as a maintenance therapy for patients with BRCA-mutated metastatic pancreatic cancer.
Olaparib is a first-in-class PARP inhibitor (authorized for marketing by both FDA and EMA in December 2014) shown to prolong progression-free survival (PFS) achieved through chemotherapy in several types of advanced cancers. Current indications include platinum-sensitive BRCA-mutated advanced ovarian, fallopian-tube, peritoneal and (selected) breast cancers. In light of the evidence presented at ASCO 2019 (median PFS = 7.4 months in treatment group vs. 3.8 months in placebo group; progression-free patients after 2 years = 1/5 in treatment group vs. 1/10 in placebo group), and of the ominous prognosis associated with metastatic pancreatic cancer – which represents the majority of newly-diagnosed pancreatic cancers –, both FDA and EMA are likely to approve the expansion of Olaparib’s therapeutic indications to include BRCA-mutated metastatic pancreatic cancer in the near future. In addition, early findings from an ongoing phase-II study, also presented at ASCO 2019, suggest Olaparib may have a similar PFS-prolonging effect in BRCA2-mutated recurrent prostate cancer.
PARP inhibitors are targeted cancer drugs that act by interfering with the PARP-mediated DNA repair pathway. This has little effect on non-cancerous cells, which still possess the BRCA-mediated DNA repair pathway, but it’s lethal for the BRCA-mutated cells making up the tumor, which become unable to restore DNA integrity and eventually undergo cell death.
Approximately 10-15% of ovarian/tubal, 5-10% of breast, 5-7% of pancreatic and 5-6% of prostate cancers are positive for inherited BRCA1/2 mutations. On the other hand, the frequency of inherited BRCA1/2 mutations in the general population has been estimated to be as high as 1:200 (0.5%), and the associated increase in the risk of developing cancer by age 70 is of 20-40x for ovarian/tubal cancer (especially for BRCA1), 5-6x for breast cancer (8x in males), 3-10x for pancreatic cancer (especially for BRCA2) and 4-8x for prostate cancer (especially for BRCA2). Genetic testing for BRCA mutations is therefore not only indicated for individuals already diagnosed with cancer – to guide targeted treatment –, but also for healthy individuals whose personal or family history suggests the possible presence of a BRCA1/2 mutation – to guide the preventive strategy (e.g. enhanced screening, prophylactic surgery).
Despite still being somewhat of a debated topic, there is growing evidence for further expansion of BRCA testing, given the cheaper and more sensitive tests being developed, the prophylactic and therapeutic options becoming available for several types of BRCA-mutated cancers and the growing concern that current inclusion criteria are insufficient to detect all BRCA mutation carriers and BRCA-mutated cancers. Improving doctors’ education and access to BRCA testing is crucial, and can in part be achieved through the use of digital tools like AZFastNet (developed by Kelyon for AstraZeneca), a web-based platform that ultimately improves patients’ access to BRCA (and EGFR) testing: AZFastNet manages the whole BRCA testing procedure – from picking up the patient sample from the hospital to delivering it to a laboratory of the AZFastNet network –, helps doctors select the laboratory that can provide the fastest results based on several parameters and live information, and makes the results quickly and easily available to the prescribing doctor.