Clinical decision making in advanced and metastatic breast cancer cases between PARP inhibitors and CDK4/6 inhibitors

Title : Clinical decision making in advanced and metastatic breast cancer cases between PARP inhibitors and CDK4/6 inhibitors

Abstract:

Background: PARP inhibitors and CDK 4/6 inhibitors have been studied extensively as model targeted agents for advanced and metastatic breast cancer with hormone receptor positive/HER2 negative molecular subtype, the most common in the patient population. Both agents have been evaluated extensively in clinical trials for clinical efficacy and toxicities and studies have proposed recommendations to overcome resistance. A comparison of the agents within each class is presented. 
Method: A PUBMED search was conducted using the keywords PARP inhibitors and Breast Cancer and CDK4/6 inhibitors AND Breast Cancer and PARP inhibitors AND Hormone Receptor Positive Tumors and PARP inhibitors AND Toxicity and BRCA1/2 mutation testing AND HR+/HER2- Advanced Breast Cancer.
Results: A number of factors, including molecular subtype, genomic characteristics, risk factors such as adverse events and potential for resistance, and evidence for desired clinical outcome must be considered in this decision making process, most impacted by the presence of the BRCA mutation and hormone receptor status and the prognostic and predictive potential of each agent. Specifically, PARP inhibitors, olaparib, talazoparib, and veriparib, should be administered if the patient is positive for the BRCA1/2 mutation. If BRCA test is negative, the three main lines of CDK4/6 inhibitors, abemaciclib, pablociclib, ribociclib, should be considered for  HR+/HER2- molecular subtypes, and the latter patient group  should be subdivided into premenopausal and postmenopausal categories. If CDK4/6 agents are not efficacious in first line settings in combination with aromatase inhibitors, there is  evidence that genomic testing for the BRCA gene could be conducted in the clinical setting post treatment and subsequently a PARP inhibitor could be administered.
Conclusion: This presentation explicitly compares these therapies for HR+/HER2- subtypes, and the finding of BRCA testing in the post clinical setting has not been proposed before after the non-efficacious administration of CDK4/6  in second line settings.

Audinence Take Away Notes:

• In a clinical scenario of locally advanced and metastatic breast cancer cases, a decision making algorithm is proposed

• The research presented will assist the audience in deciding between PARP inhibitors and CDK4/6 inhibitors for HR+/HER2- molecular subtypes

• Drug developers would benefit from the discussion of adverse events and drug resistance in the presentation

Biography:

Priya Hays, M.S., Ph.D. is an accomplished science writer, having written and published five books as well as having authored over twenty publications in journals as varied as the Bulletin of Science, Technology and Society, L’Esprit Createur, Interdisciplinary Literary Studies, Genetics in Medicine, Journal of Clinical Investigation and Studies, and Preventive Medicine, Epidemiology and Public Health. She is served as Guest Editor for a volume on cancer immunotherapies in the Cancer Treatment and Research series. Her most recent book is a compilation of papers entitled “A Dialectical Mind: Essays in Literary Studies, Science and Medicine” published by Eliva Press. She completed her postdoctoral research fellowship in the Division of Hematology/Oncology, Department of Medicine, at Dartmouth Medical School. She has an A.B. with Honors from Dartmouth College in Biochemistry and Comparative Literature, an M.S. in Genetics from the University of California, Davis, and a Ph.D. in Literature from the University of California, San Diego.