Sunday, March 25, 2018, New Orleans, LA, 12:00 PM – 1:30 PM

Beyond the Guidelines: Investigator Perspectives on the Current and Future Role of PARP Inhibition in the Management of Ovarian Cancer

An Independent CME Satellite Symposium During the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer

Location:
Hyatt Regency New Orleans
601 Loyola Avenue
New Orleans, LA 70113
Phone: (504) 613-3933

Event Time (Central Time):
11:30 AM – 12:00 PM — Registration and Lunch Buffet
12:00 PM – 1:30 PM — Educational Meeting

Meeting Room:
Empire Ballroom A (Level 2)

There is no registration fee for this event. However, preregistration is advised as seating is limited.

Faculty:
Robert L Coleman, MD
Professor and Vice Chair, Clinical Research
Ann Rife Cox Chair in Gynecology
Department of Gynecologic Oncology and Reproductive Medicine
The University of Texas MD Anderson Cancer Center
Houston, Texas

Joyce F Liu, MD, MPH
Assistant Professor of Medicine
Gynecologic Oncology Program
Susan F Smith Center for Women's Cancers
Dana-Farber Cancer Institute
Boston, Massachusetts

Mansoor Raza Mirza, MD
Medical Director
Nordic Society of Gynecologic Oncology
Chief Oncologist, Department of Oncology
Rigshospitalet, Copenhagen University Hospital
Copenhagen, Denmark

Kathleen Moore, MD
Jim and Christy Everest Endowed Chair in Cancer Research
Director, Oklahoma TSET Phase I Program
Stephenson Cancer Center
Associate Professor, Section of Gynecologic Oncology
Director, Gynecologic Oncology Fellowship
Department of Obstetrics and Gynecology
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma

Moderator:
Neil Love, MD
Research To Practice
Miami, Florida



MODULE 1: Biologic Rationale for PARP Inhibition in Ovarian Cancer (OC); Current Genetic Testing Algorithms — Dr Coleman

SAMPLE CONSENSUS-BUILDING/INVESTIGATOR SURVEY QUESTIONS
  • At what point do you generally conduct genetic testing? What specific testing platform(s) do you use at your institution? Would you recommend the same modality to a gynecologic oncologist practicing in the community?
  • Do cancers with somatic BRCA mutations behave similarly to those harboring a germline defect? Do you assess the presence of a somatic alteration as part of initial testing or look for this specific mutation after an initial germline BRCA assessment returns negative?
  • Do you currently attempt to assess the presence of other mutations or genomic abnormalities (eg, RAD51C, RAD51D, BRIP1) for your patients with newly diagnosed or recurrent OC? Which of these aberrations, if any, would compel you to recommend the use of a PARP inhibitor outside of a clinical trial?
  • Are you currently screening any of your patients with OC for homologous recombination deficiency (HRD), and, if so, what specific assay do you use? Do you believe these cancers behave similarly to those harboring a BRCA mutation, and do you generally manage them in a similar manner?
Faculty Presentation/Panel Discussion Topics
  • Frequency and clinical significance of germline and somatic BRCA mutations
  • Similarities and differences among available genetic testing platforms; role of extended panel testing/next-generation sequencing
  • Identification of “BRCA-like” and other genomic signatures (eg, HRD) that may predict benefit from PARP inhibition
  • Indications for repeat testing to identify patients with tumor transformation (eg, HRD-negative on archival tissue but HRD-positive on fresh biopsy)
  • Incidence and potential clinical relevance of other inherited mutations (eg, RAD51C, RAD51D, BRIP1)
  • Rates and clinical implications of variants of unknown significance

MODULE 2: Current Role of PARP Inhibition in the Management of Recurrent OC — Dr Liu

SAMPLE CONSENSUS-BUILDING/INVESTIGATOR SURVEY QUESTIONS
  • A 60-year-old woman with a BRCA germline mutation is s/p optimal debulking surgery for Stage IIIC epithelial OC (EOC). She completes 6 cycles of carboplatin/paclitaxel but 12 months later experiences disease progression. What therapy would you recommend at this point?
  • The patient in the previous question receives 6 cycles of carboplatin/pegylated liposomal doxorubicin, and repeat imaging shows a complete response (CR). What maintenance therapy, if any, would you recommend? What if she had a partial response (PR)? Would your treatment recommendation change if the patient had received bevacizumab (bev)?
  • A 60-year-old woman with BRCA wild-type OC is s/p optimal debulking surgery for Stage IIIC EOC. She completes 6 cycles of carboplatin/paclitaxel but 12 months later experiences disease progression. The patient then receives 6 cycles of carboplatin/paclitaxel/bev, and repeat imaging shows a CR. What maintenance therapy, if any, would you recommend? Would your treatment recommendation change if the patient had not received bev? What if the patient had a PR to her primary therapy?
  • A 60-year-old woman with a BRCA germline mutation is s/p optimal debulking surgery and adjuvant chemotherapy with carboplatin/paclitaxel but experiences disease progression 5 months after completion of adjuvant therapy. She receives weekly paclitaxel/bev and subsequently develops progressive disease after 4 months of therapy. What is your most likely systemic treatment recommendation at this point?
Faculty Presentation/Panel Discussion Topics
  • FDA indications for and optimal integration of niraparib, olaparib and rucaparib into contemporary OC treatment algorithms
  • Design, eligibility requirements and results from the Phase III NOVA (niraparib), SOLO-2 (olaparib) and ARIEL-3 (rucaparib) trials evaluating PARP inhibition as maintenance therapy in patients with platinum-sensitive OC
  • Stratification and related outcomes for various patient subsets (eg, BRCA mutation-positive, HRD-positive, wild-type) enrolled on Phase III PARP inhibitor maintenance trials
  • Response rates observed in Phase III PARP inhibitor maintenance trials based on prior lines of therapy or response to primary chemotherapy; implications, if any, for routine clinical practice
  • Emerging research information on the relationship between PARP inhibitor exposure/dosing and efficacy

MODULE 3: Unique Tolerability Considerations Associated with PARP Inhibitors — Dr Moore

SAMPLE CONSENSUS-BUILDING/INVESTIGATOR SURVEY QUESTIONS
  • A 60-year-old woman with a BRCA germline mutation is started on olaparib, and after 6 weeks her hemoglobin has dropped from 11.0 to 8.8 g/dL with no evidence of hemolysis or bleeding. CA125 has decreased from 350 to 150. In addition to supportive measures such as erythropoiesis-stimulating agents, what would be your most likely initial management approach?
  • A patient with recurrent EOC and a deleterious BRCA germline mutation has received 3 lines of chemotherapy and is currently receiving olaparib and responding. However, she experiences gastrointestinal (GI) toxicity, which is not ameliorated with treatment or dose reduction. Would you consider switching the patient to another PARP inhibitor? In general, when you administer a PARP inhibitor, do you initiate preemptive medication for nausea and vomiting or wait until the patient begins to exhibit these effects?
  • A 60-year-old woman with recurrent high-grade serous OC is started on rucaparib (600 mg BID). During the second cycle, serum creatinine increases from 0.8 mg/dL to 1.83 mg/dL. What would be your most likely management approach?
  • A 65-year-old woman with advanced OC is started on standard-dose niraparib. Her pretreatment platelet count is 220,000 but drops to 90,000 after 10 days of treatment. What would be your most likely approach? Assuming therapy was stopped and her platelets started to normalize, at what point, if any, would you consider reintroducing the niraparib (and at what dose)?
Faculty Presentation/Panel Discussion Topics
  • GI toxicities associated with the use of available PARP inhibitors and strategies to prevent and/or ameliorate them; role of dose adjustments and delays in individuals experiencing significant GI side effects
  • Incidence and timing of hematologic toxicities observed in patients receiving PARP inhibitors; recommended monitoring protocols and indications for the use of supportive care measures and/or treatment modifications/delays
  • Incidence, timing and severity of hypertension associated with the use of niraparib in the maintenance setting
  • Mechanism of and monitoring for elevated liver enzymes in patients receiving rucaparib; thresholds for active intervention
  • Other adverse events of interest documented with PARP inhibitors (eg, elevated creatinine, acute myeloid leukemia/myelodysplastic syndromes, pneumonitis, elevated cholesterol, photosensitivity/rash)

MODULE 4: Investigational Applications of Approved PARP Inhibitors; Other Novel PARP Inhibitors in Clinical Development — Dr Mirza

SAMPLE CONSENSUS-BUILDING/INVESTIGATOR SURVEY QUESTIONS
  • Based on available data and your own clinical experience, what would you predict that a clinical trial evaluating current standard therapy versus current standard therapy combined with or followed by a PARP inhibitor for patients who are s/p optimal debulking surgery would show? Are you prioritizing enrollment in any of these trials for your own patients?
  • Do you believe veliparib or talazoparib will offer significant efficacy or safety advantages over the other PARP inhibitors already available in the clinic?
  • Are there any situations in which you believe it is currently acceptable to combine a PARP inhibitor with chemotherapy outside of a clinical trial? What about a PARP inhibitor with an anti-VEGF agent?
  • Is there a biologic rationale for potential synergy between PARP inhibition and immune checkpoint inhibition?
Faculty Presentation/Panel Discussion Topics
  • Mechanisms of PARP inhibitor resistance, including the emergence of BRCA reversion mutations; implications for future research and clinical practice
  • Mechanistic similarities and differences between approved and other PARP inhibitors in clinical development — talazoparib and veliparib
  • Available efficacy and safety data with and ongoing studies evaluating talazoparib and veliparib for patients with advanced EOC
  • Early efficacy and tolerability data with PARP inhibitors in combination with chemotherapy and/or anti-angiogenic agents; late-stage clinical trials evaluating these approaches
  • Biologic rationale and eligibility criteria for ongoing trials of PARP inhibitors combined with immune checkpoint inhibitors

Target Audience:
This activity is intended for gynecologic oncologists, medical oncologists, gynecologists and other healthcare providers involved in the treatment of gynecologic cancers.

Learning Objectives:
Upon completion of this activity, participants should be able to:

  • Compare and contrast the diagnostic and therapeutic recommendations made by gynecologic cancer clinical investigators for patients with ovarian cancer (OC), and use this information to guide the integration of PARP inhibitors into the care of appropriate individuals.
  • Appraise available guideline recommendations and consensus statements regarding the indications and evidence-based modalities for genetic testing in OC, and use the results of these assessments to guide long-term treatment planning.
  • Appreciate available clinical trial data with, approved indications for and common toxicities resulting from the use of FDA-endorsed PARP inhibitors for patients with OC to safely integrate these agents into routine clinical practice.
  • Consider available clinical trial data with PARP inhibitors as maintenance therapy for recurrent, platinum-sensitive OC, and develop strategies to incorporate this approach into current management algorithms.
  • Develop an understanding of the mechanisms of action, available data and potential clinical roles of other investigational PARP inhibitors in preparation for their potential introduction into future OC clinical practice.
  • Recognize the biologic rationale for, available data with and ongoing investigations of PARP inhibitors in combination with chemotherapy, biologic therapy and immunotherapy, and refer appropriate patients for clinical trial participation.

CME Credit Form:
A credit form will be given to each participant at the conclusion of this activity.

Accreditation Statement:
Research To Practice is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

Credit Designation Statement:
Research To Practice designates this live activity for a maximum of 1.5 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Disclosure Policy:
Research To Practice (RTP) is committed to providing its participants with high-quality, unbiased and state-of-the-art education. We assess conflicts of interest with faculty, planners and managers of CME activities. Conflicts of interest are identified and resolved through a conflict of interest resolution process. In addition, all activity content is reviewed by both a member of the RTP scientific staff and an external, independent physician reviewer for fair balance, scientific objectivity of studies referenced and patient care recommendations. Financial disclosures will be provided in meeting course materials.

Supporters:
This activity is supported by educational grants from AbbVie Inc, AstraZeneca Pharmaceuticals LP, Clovis Oncology, Myriad Genetic Laboratories Inc and Tesaro Inc.

Hyatt Regency New Orleans
601 Loyola Avenue
New Orleans, LA 70113
Phone: (504) 613-3933

Meeting Room:
Empire Ballroom A (Level 2)

Directions:
The Hyatt Regency New Orleans hotel is the main venue for the SGO Annual Meeting on Women's Cancer.

 
Thank you for your interest in our educational program. At this time online registration is closed. However, seats are still available for the meeting.

If you are interested in attending, please visit our onsite registration desk located outside the Empire Ballroom A (Level 2) of the Hyatt Regency New Orleans (601 Loyola Avenue). Our onsite registration desk will be open starting at 11:00 AM on Sunday, March 25, 2018.

We will accept new registrations on a first come, first served basis. If you have any questions, please feel free to contact us via email at Meetings@ResearchToPractice.com or call (800) 233-6153.

NOTICE:
Registration for this event is independent of registration for the Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer.