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A New Frontier in Cancer Therapy: Examining the Role of PARP Inhibitors in an Emerging Paradigm

This CPE activity is based on the slides and lectures presented by the faculty at an independent satellite symposium during the Hematology/Oncology Pharmacy Association's 15th Annual Conference on Friday, April 5, 2019, at the Fort Worth Convention Center in Fort Worth, Texas.

Release Date

June 17, 2019

Expiration Date

June 17, 2020

Faculty

Jason Bergsbaken, PharmD, BCOP
Pharmacy Coordinator
Regional Oncology Services 
University of Wisconsin Hospital and Clinics
Madison, Wisconsin

Nadine Tung, MD
Chief, Breast Oncology 
Director, Cancer Genetics and Prevention Program
Beth Israel Deaconess Medical Center
Associate Professor of Medicine
Harvard Medical School
Boston, Massachusetts

Needs Statement

Many contemporary approaches to cancer therapy are predicated on targeting molecular pathways that are present in tumor cells but absent in healthy cells; one such pathway, the DNA damage response (DDR) pathway, forms the mechanistic rationale behind poly ADP-ribose polymerase (PARP) inhibition as a novel treatment strategy. DDR deficiencies result in genomic instability—a clinical hallmark of cancer—and increase cellular reliance on compensatory repair pathways.¹ PARP inhibitors are oral medications designed to inhibit these alternative repair mechanisms, thereby achieving “synthetic lethality,” or eventual apoptosis of the DDR-deficient cancer cell.² Clinical trials have demonstrated significant efficacy outcomes with PARP inhibition in BRCA-mutated malignancies. Though the greatest clinical benefit has thus far been seen in breast and ovarian cancers, data are still evolving regarding the utility of PARP inhibition in other cancers, most notably prostate and pancreatic disease.^3–6 While these novel agents have broadened treatment horizons and enhanced patient flexibility with oral dosing, they also pose myriad patient education challenges for clinicians. Oncology pharmacists, as frontline caregivers with expertise in the pharmacokinetic, pharmacodynamic, and economic aspects of oral chemotherapy, are optimally placed to help patients understand their medication regimen, treatment goals, and potential side effects, as well as promote adherence and combat “financial toxicity.”⁷

Learners will explore the new frontier of PARP inhibition in cancer therapy, including the latest advances in targeting the DDR pathway, as well as current and emerging trial data for PARP inhibitors in breast, ovarian, prostate, and pancreatic cancers. Using case-based strategies, faculty will evaluate clinical challenges and propose innovative methodologies by which oncology pharmacists can manage adverse events, enhance adherence, and optimize outcomes for patients taking PARP inhibitors.

¹Hoeijmakers JH. Nature. 2001; ²Kaelin WG. Nat Rev Cancer. 2005; ³Watkins JA, et al. Breast Cancer Res. 2014; ⁴Balmana J, et al. Ann Oncol. 2014; ⁵Del Conte GC, et al. Br J Cancer. 2014; ⁶Livraghi L, et al. BMC Med. 2015; ⁷Burhenn PS, et al. Clin J Oncol Nurs. 2015.

Target Audience

This activity is designed to meet the educational needs of pharmacists with an interest in hematology/oncology, oncology pharmacists, pharmacy directors, and pharmacy residents.

Objectives

At the conclusion of this enduring activity, participants will be able to:

1. Analyze key DNA damage repair pathways and discuss how mechanistic deficiencies in these pathways can contribute to tumor proliferation and uncontrolled growth.
2. Examine the mechanism of action of PARP inhibitors and assess how their innovative pharmacology exploits the concept of “synthetic lethality” in BRCA-mutated cells, and in those with “BRCAness” features.
3. Investigate burgeoning trial data regarding the safety and efficacy profiles of currently-approved PARP inhibitors and those still in clinical development for the treatment of ovarian, breast, prostate, and pancreatic cancers.
4. Using case-based strategies, evaluate challenging clinical scenarios involving PARP inhibitors and propose innovative ways the pharmacist can optimize therapy, anticipate and manage adverse events, and promote patient adherence.

Accreditation

ACPE
In support of improving patient care, Creative Educational Concepts is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

This application-based activity is approved for 1.0 contact hour of continuing pharmacy education credit (JA0007101-0000-19-007-H01-P).

Other

Creative Educational Concepts, Inc. certifies this activity for 1.0 hour of participation.

Faculty Disclosure

Planner and Faculty Disclosures

In accordance with the Food and Drug Administration, the speakers have disclosed that there is the potential for discussions concerning off-label uses of a commercial product/device during this educational activity.

Any person who may contribute to the content of this continuing education activity must disclose relevant relationships (and any known relationships of their spouse/partner) with commercial interests whose products or services are discussed in educational presentations. A commercial interest is defined as any entity producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients. Relevant relationships include receiving from a commercial interest research grants, consultant fees, travel, other benefits, or having a self-managed equity interest in a company.

Disclosure of a relationship is not intended to suggest or condone any bias in any presentation but is made to provide participants with information that might be of potential importance to their evaluation of a presentation.

Planners

Bryan Taylor, PharmD—has no relevant financial relationships to disclose in relation to the content of this activity.

Authors/Presenters

Jason Bergsbaken, PharmD, BCOP—has no relevant financial relationships to disclose in relation to the content of this activity.

Nadine M. Tung, MD—has disclosed that she receives grant/research support from AstraZeneca.

Peer Reviewers

Laura Alwan, PharmD, BCOP—has no relevant financial relationships to disclose in relation to the content of this activity.

Activity Instructions

Media: Internet Web Activity (PowerPoint slides and audio)

Instructions:

To receive a statement of credit, you must:

1. Read the target audience, learning objectives, and author disclosures.
2. Review the full content of the activity and reflect upon its teaching.
3. Complete the questions and evaluation at the end of the activity.
4. You must have a passing score of 75% on the post-test. You will have two (2) opportunities to complete the post-test.