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:
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In a clinical scenario of locally advanced and metastatic breast cancer cases, a decision making algorithm is proposed
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The research presented will assist the audience in deciding between PARP inhibitors and CDK4/6 inhibitors for HR+/HER2- molecular subtypes
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Drug developers would benefit from the discussion of adverse events and drug resistance in the presentation
