Community Practice Connections™: Advances in Ovarian Cancer: Evolving Applications for PARP Inhibitors, Immunotherapy & Beyond!

Release Date: August 30, 2019
Expiration Date: August 30, 2020
Media: Internet - based

Activity Overview

In the management ovarian cancer following prior platinum-based chemotherapy, poly(ADP-ribose) polymerase (PARP) inhibitors have an important role in reducing the risk of recurrence. Understanding the approved uses of these agents in the frontline maintenance setting and later-line settings is crucial to implementing evidence-based use of these treatments. Recognizing the mechanistic characteristics of these treatments, their appropriate use across patient subgroups, and ongoing trials help inform clinical practice. In addition, managing adverse events with these therapies and recognizing the potential for further development with PARP inhibitors in combination with other agents remains an important priority. This online program features expert commentary from top experts in ovarian cancer and summarizes key takeaways presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting.

Benefits of Participating

• Learn best practices in the use of poly(ADP-ribose) polymerase (PARP) inhibitors in ovarian cancer directly from top experts in the field
• Evaluate practice-changing clinical trial results instrumental to the approval of PARP inhibitors in ovarian cancer
• Recognize appropriate populations and clinical scenarios for use of PARP inhibitors based on clinical trial data
• Review adverse events associated with PARP inhibitors, contrast the adverse event profile of agents in this class, and learn best practices for monitoring and management of potential adverse events
• Evaluate the design and preliminary results of ongoing studies evaluating PARP inhibitors in combination with other agents

Acknowledgement of Commercial Support

This activity is supported by educational grants from AstraZeneca, Merck & Co, Inc, and TESARO.

Target Audience

This educational program is directed toward the ASCO Annual Meeting audience, including medical oncologists, gynecologic oncologists, pathologists, radiation oncologists, and surgical oncologists. Other attendees of the ASCO Annual Meeting who have an interest in the treatment of ovarian cancer, such as obstetrician-gynecologists, nurses, physician assistants, fellows, and residents, are also invited to participate.

Learning Objectives

Upon successful completion of this educational activity, you should be better prepared to:

• Summarize key safety and efficacy outcomes from clinical trials that have evaluated PARP inhibitors for ovarian cancer management
• Examine evidence related to the timing and selection of molecular testing methods for patients with ovarian cancer
• Outline recent data on emerging approaches for the management of patients with ovarian cancer
• Identify practical strategies to manage adverse events encountered with the use of emerging therapeutic options for patients with ovarian cancer

Faculty, Staff, and Planners’ Disclosures

Faculty

Michael J. Birrer, MD, PhD
Director, O’Neal Comprehensive Cancer Center
The University of Alabama at Birmingham
Professor of Medicine, Obstetrics/Gynecology, and Pathology
Evalina B. Spencer Endowed Chair in Oncology
Birmingham, AL

Disclosures: Michael Birrer, MD, PhD, has no relevant financial relationships with commercial interests to disclose.

Robert L. Coleman, MD, FACOG, FACS
Professor and Executive Director, Cancer Network Research
Ann Rife Cox Chair in Gynecology
Department of Gynecologic Oncology and Reproductive Medicine
The University of Texas MD Anderson Cancer Center
Houston, TX

Disclosures: Grant Research Support: AstraZeneca, Clovis Oncology, Genentech-Roche, Janssen, Merck; Consultant: AbbVie, Cell Medica, COR2ED, Geistlich, Genmab, MORE Health, Takeda, TESARO; Speakers Bureau: Roche; Shareholder: MORE Health; Other: Scientific/Advisory Board: Aravive Biologics, Inc; ArQule; AstraZeneca; Clovis Oncology; Eisai Medical Research; Genentech, Inc; Merck; Mersana Therapeutics, Inc; Myriad; National Comprehensive Cancer Network; Novocure; OncoMed Pharmaceuticals, Inc; TESARO.

Ursula A. Matulonis, MD
Director and Chief, Division of Gynecologic Oncology
Brock-Wilson Family Chair
Dana-Farber Cancer Institute
Professor of Medicine
Harvard Medical School
Boston, MA

Disclosures: Grant Research Support: Merck; Consultant: Merck, Immunogenics.

Kathleen Moore, MD
Virginia Kerley Cade Chair in Developmental Therapeutics
Associate Director, Clinical 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, OK

Disclosures: Grant Research Support: PTC Therapeutics, Genentech/Roche, Merck, Clovis, Lilly; Consultant: AstraZeneca, Clovis, Aravive, Samumed, OncoMed, Genentech/Roche, TESARO, ImmunoGen, Pfizer, Merck, Janssen.

The staff of Physicians' Education Resource^®, LLC (PER^®), have no relevant financial relationships with commercial interests to disclose.

Disclosure Policy and Resolution of Conflicts of Interest (COI)

As a sponsor accredited by the ACCME, it is the policy of PER^® to ensure fair balance, independence, objectivity, and scientific rigor in all of its CME activities. In compliance with ACCME guidelines, PER^® requires everyone who is in a position to control the content of a CME activity to disclose all relevant financial relationships with commercial interests. The ACCME defines relevant financial relationships as financial relationships in any amount occurring within the past 12 months that create a COI.

Additionally, PER^® is required by ACCME to resolve all COI. PER^® has identified and resolved all COI prior to the start of this activity by using a multistep process.

Off-Label Disclosure and Disclaimer

This CME activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this CME activity is for continuing medical and nursing education purposes only and is not meant to substitute for the independent clinical judgment of a physician and nurse relative to diagnostic or treatment options for a specific patient’s medical condition.

The opinions expressed in the content are solely those of the individual faculty members and do not reflect those of PER^® or any of the companies that provided commercial support for this activity.

PER Pulse^™ Recaps

1 of 3

Insight from Kathleen Moore, MD—PER Pulse™ Recap:
Community Practice Connections™: Advances in Ovarian Cancer: Evolving Applications for PARP Inhibitors, Immunotherapy & Beyond!

Community Practice Connections™: Advances in Ovarian Cancer: Evolving Applications for PARP Inhibitors, Immunotherapy & Beyond! is a continuing medical education–certified program. For this program, chair Robert L. Coleman, MD, FACOG, FACS, was joined by expert faculty Kathleen Moore, MD, Ursula A. Matulonis, MD, and Michael J. Birrer, MD, PhD, to discuss the latest data in ovarian cancer regarding the use of PARP inhibitors.

This first of 3 PER Pulse™ Recaps summarizing the online activity focuses on strategies for individualizing decision making regarding appropriate use of PARP inhibitors in patients with ovarian cancer. Below are some highlights from the activity featuring Dr Moore:

• All 3 PARP inhibitors approved for use in ovarian cancer—olaparib, niraparib, and rucaparib—are approved for use in the treatment of adult patients with BRCA-mutated advanced ovarian cancer.^1-3
  • Olaparib is approved for maintenance treatment in patients with germline and somatic BRCA mutations, as well as patients with wild-type disease, following a complete or partial response to first-line platinum-based chemotherapy. Olaparib is also approved for use in patients with germline BRCA-mutated advanced ovarian cancer who have been treated with 3 or more prior lines of chemotherapy.¹
  • Like olaparib, rucaparib is approved for maintenance treatment in adult patients with ovarian cancer who are in a complete or partial response to platinum-based chemotherapy. However, unlike olaparib, rucaparib is indicated for use in both patients with germline and those with somatic BRCA mutations who have been treated with 2 or more prior lines of chemotherapeutic regimens.²
  • The indication statement for niraparib is more general than that of olaparib or rucaparib. Niraparib is currently approved for the maintenance treatment of adult patients who are in a complete or partial response to platinum-based chemotherapy.³
• Completed studies with PARP inhibitors to date show the benefit of using PARP inhibitors across a wide range of patients with ovarian cancer, including patients with BRCA-associated ovarian cancer, as demonstrated in the SOLO2, NOVA, and ARIEL3 trials. However, benefits beyond BRCA have also been observed, including in study 19, a subgroup of patients in the NOVA study, and subgroups of patients in ARIEL3.^4-7

“For patients who are treated with repeat induction platinum-based chemotherapy and have complete or partial response to that therapy, all 3 PARP inhibitors—olaparib, niraparib, and rucaparib—are approved as maintenance therapy.”
—Kathleen Moore, MD

References

1. Olaparib Package Insert. https://www.azpicentral.com/lynparza_tb/lynparza_tb.pdf#page=1. Published Accessed June 12, 2019.
2. Rucaparib Package Insert. https://clovisoncology.com/media/1094/rubraca-prescribing-info.pdf. Accessed June 12, 2019.
3. Niraparib Package Insert. Zejula_niraparib__Feb_2019.pdf. https://www.zejula.com/prescribing-information. Accessed June 12, 2019.
4. Ledermann J, Harter P, Gourley C, et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med. 2012;366(15):1382-1392. doi: 10.1056/NEJMoa1105535.
5. Pujade-Lauraine E, Ledermann JA, Selle F, et al; SOLO2/ENGOT-Ov21 investigators. Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial [erratum in Lancet Oncol. 2017;18(9):e510]. Lancet Oncol. 2017;18(9):1274-1284. doi: 10.1016/S1470-2045(17)30469-2.
6. Mirza MR, Monk BJ, Herrstedt J, et al. Niraparib maintenance therapy in platinum-sensitive, recurrent ovarian cancer. N Engl J Med. 2016;375(22):2154-2164. doi: 10.1056/NEJMoa1611310.
7. Coleman RL, Oza AM, Lorusso D, et al. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial [erratum in Lancet. 2017;390(10106):1948]. Lancet. 2017;390(10106):1949-1961. doi: 10.1016/S0140-6736(17)32440-6.

2 of 3

Insight from Ursula A. Matulonis, MD—PER Pulse™ Recap:
Community Practice Connections™: Advances in Ovarian Cancer: Evolving Applications for PARP Inhibitors, Immunotherapy & Beyond!

Community Practice Connections™: Advances in Ovarian Cancer: Evolving Applications for PARP Inhibitors, Immunotherapy & Beyond! is a continuing medical education–certified program. For this program, chair Robert L. Coleman, MD, FACOG, FACS, was joined by expert faculty Ursula A. Matulonis, MD, Kathleen Moore, MD, and Michael J. Birrer, MD, PhD, to discuss the latest data in ovarian cancer regarding the use of PARP inhibitors.

This second of 3 PER Pulse™ Recaps summarizing the online activity focuses on strategies for individualizing decision making regarding appropriate use of PARP inhibitors in patients with ovarian cancer. Below are some highlights from the activity featuring Dr Matulonis:

• PARP inhibitors exert multiple effects on the complex PARP enzyme system. In addition to repairing DNA damage, PARP enzymes function in transcription regulation, immune regulation, and regulation of inflammatory processes. PARP inhibitors work by inhibiting loss of base excision repair, leading to reliance on double-strand break repair. Double-strand break repair is less efficient in patients with BRCA mutations, improving efficacy. Beyond this mechanism, PARP trapping also has an important role in the efficacy of these agents.^1,2
• One of the most important studies with PARP inhibitors in recent years was the SOLO-1 study, adding olaparib maintenance therapy following chemotherapy in women with underlying BRCA mutations who had previously received carboplatin/paclitaxel combination therapy. Progression-free survival results as assessed by investigators showed a 70% reduction in risk of disease progression or death with olaparib maintenance therapy (HR, 0.30; 95% CI, 0.23-0.41; P <.0001). Importantly, after 3 years of follow-up, 60.4% of patients receiving olaparib versus 26.9% of patients randomized to placebo were free of progression.³
• In SOLO-1, serious adverse events (AEs) occurred in 20.8% versus 12.3% of patients. Treatment-emergent AEs leading to dose reductions (28.5% with olaparib vs 3.1% with placebo) and discontinuations of therapy (11.5% with olaparib vs 2.3% with placebo) were more frequent in the treatment group. AEs of special interest occurring in olaparib-treated patients versus placebo included myelodysplastic syndrome (1.2% vs 0%) and new primary malignancies (1.9% vs 2.3%).³

“SOLO-1 has made standard of care the use of olaparib in women with BRCA-mutated ovarian cancer in response to platinum-based chemotherapy.”
—Ursula A. Matulonis, MD

References:

1. Konstantinopoulos PA, Matulonis UA. PARP inhibitors in ovarian cancer: a trailblazing and transformative journey. Clin Cancer Res. 2018;24(17):4062-4065. doi: 10.1158/1078-0432.CCR-18-1314.
2. Thomas A, Murai J, Pommier Y. The evolving landscape of predictive biomarkers of response to PARP inhibitors. J Clin Invest. 2018;128(5):1727-1730. doi: 10.1172/JCI120388.
3. Moore K, Colombo N, Scambia G, et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N Engl J Med. 2018;379(26):2495-2505. doi: 10.1056/NEJMoa1810858.

3 of 3

Insight from Michael J. Birrer, MD, PhD—PER Pulse™ Recap:
Community Practice Connections™: Advances in Ovarian Cancer: Evolving Applications for PARP Inhibitors, Immunotherapy & Beyond!

Community Practice Connections™: Advances in Ovarian Cancer: Evolving Applications for PARP Inhibitors, Immunotherapy & Beyond! is a continuing medical education–certified program. For this program, chair Robert L. Coleman, MD, FACOG, FACS, was joined by expert faculty Michael J. Birrer, MD, PhD, Ursula A. Matulonis, MD, and Kathleen Moore, MD, to discuss the latest data in ovarian cancer regarding the use of PARP inhibitors.

This third of 3 PER Pulse™ Recaps summarizing the online activity focuses on strategies for individualizing decision making regarding appropriate use of PARP inhibitors in patients with ovarian cancer. Below are some highlights from the activity featuring Dr Birrer:

• PARP inhibition in combination with antiangiogenic therapy is currently under evaluation in the phase II AVANOVA study, interim results of which were reported at the 2019 American Society of Clinical Oncology Annual Meeting. In this randomized, open-label, phase II study, women with measurable/evaluable, high-grade serous or endometrioid platinum-sensitive recurrent ovarian cancer received niraparib 300 mg daily or combination therapy with niraparib 300 mg daily plus bevacizumab 15 mg/kg intravenously every 3 weeks until disease progression. Combination therapy significantly improved progression-free survival (PFS) compared with single-agent niraparib (median PFS, 11.9 vs 5.5 months; adjusted HR, 0.35; P <.001).¹
• Interim results of the phase II SOLO3 study, which included patients receiving olaparib versus physician’s choice nonplatinating chemotherapy in the relapsed setting in patients who experience relapse following at least 2 prior lines of platinum-based chemotherapy. This study includes patients with no prior use of PARP inhibitors and a documented BRCA mutation in the treatment setting. In this study, a PFS benefit was identified by blinded reviewers (median PFS, 13.4 vs 9.2 months; HR, 0.62; P = .013) and by investigator assessment (median PFS, 13.2 vs 8.5 months; HR, 0.49; P = .001).²
• In the phase III randomized, double-blind, multicenter ANITA study, the combination of atezolizumab and platinum-based doublet therapy followed by maintenance niraparib versus placebo plus platinum-based doublet therapy is currently being evaluated in patients with recurrent high-grade serous or endometrioid ovarian cancer. Patients enrolled in the study were required to have an ECOG performance status of 0 or 1, a known BRCA status, at least 1 measurable lesion, and ≤2 prior lines of therapy. Patients were stratified by prior platinum-based regimen, the duration of their platinum-free interval (ie, 6-12 months vs >12 months), and BRCA status (ie, mutated vs nonmutated).³

“I hold out a lot of enthusiasm for the combination of antiangiogenic agents plus PARP inhibitors.”
—Michael J. Birrer, MD, PhD

References:

1. Mirza MR, Avall-Lundqvist E, Birrer MJ, et al. Combination of niraparib and bevacizumab versus niraparib alone as treatment of recurrent platinum-sensitive ovarian cancer: a randomized controlled chemotherapy-free study—NSGO-AVANOVA2/ENGOT-OV24. J Clin Oncol. 2019;37(suppl 15; abstr 5505). ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.5505. Accessed June 12, 2019.
2. Penson RT, Valencia RV, Cibula C, et al. Olaparib monotherapy versus (vs) chemotherapy for germline BRCA-mutated (gBRCAm) platinum-sensitive relapsed ovarian cancer (PSR OC) patients (pts): phase III SOLO3 trial. J Clin Oncol. 2019;37(suppl 15):5506. ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.5506. Accessed June 12, 2019.
3. González-Martín A, Colombo N, Heitz F, et al. ENGOT-Ov41/GEICO-69-O/ANITA trial: a phase III randomized, double-blinded trial of platinum-based chemotherapy (CT) with or without atezolizumab (ATZ) followed by niraparib maintenance with or without ATZ in patients with recurrent ovarian, tubal or peritoneal cancer (OC) and platinum treatment-free interval (TFIp) >6 months Presented at: 2019 American Society of Clinical Oncology Annual Meeting; June 1, 2019; Chicago, IL. Abstract TPS5599. abstracts.asco.org/239/AbstView_239_252727.html. Accessed June 12, 2019.