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Maintenance Therapy for Ovarian Cancer: Practical Considerations for Community Practice

  • Authors: Ursula Matulonis, MD; Lyndsay Willmott, MD; Terry Jannuzzo
  • CME / ABIM MOC Released: 3/28/2019
  • Valid for credit through: 3/28/2020, 11:59 PM EST
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Target Audience and Goal Statement

This activity is intended for community practice-based oncologists and gynecologic oncologists who manage patients with ovarian cancer.

The goal of this symposium is to improve the knowledge of community-based oncologists on the most up-to-date clinical trial data on poly (ADP-ribose) polymerase (PARP) inhibitors and the antiangiogenic agent bevacizumab in maintenance therapy for patients with advanced ovarian cancer to increase their competence and confidence in the optimal use of maintenance therapy in these patients.

Upon completion of this activity, participants will:

  • Have increased knowledge regarding the
    • Clinical trial safety and efficacy data evaluating PARP inhibitors and antiangiogenics as maintenance therapy in ovarian cancer
    • Practical approaches to overcoming barriers to utilizing maintenance therapy in the management of advanced ovarian cancer in community practice
  • Have greater competence related to
    • Identifying patients with advanced ovarian cancer who are candidates for maintenance therapy
  • Demonstrate greater confidence in their ability to
    • Communicate effectively with patients about maintenance therapy for advanced ovarian cancer in order to involve them in shared decision-making


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  • Ursula Matulonis, MD

    Professor of Medicine
    Harvard Medical School
    Director and Chief, Division of Gynecologic Oncology
    Brock-Wilson Family Chair
    Dana-Farber Cancer Institute
    Boston, Massachusetts


    Disclosure: Ursula Matulonis, MD, has disclosed the following relevant financial relationships:
    Served as an advisor or consultant for: 2X Oncology, Inc.; Geneos Therapeutics, Inc.; Immunogen, Inc.; Mersana Therapeutics, Inc.
    Received grants for clinical research from: Merck & Co., Inc.

  • Terry Jannuzzo

    Ovarian Cancer Survivor/Advocate
    Dutchess County, New York


    Disclosure: Terry Jannuzzo has disclosed the following relevant financial relationships:
    Patient assistance program: AstraZeneca Pharmaceuticals LP

  • Lyndsay Willmott, MD

    Gynecologic Oncologist
    Arizona Oncology
    Phoenix, Arizona


    Disclosure: Lyndsay Willmott, MD, has disclosed the following relevant financial relationships:
    Served as an advisor or consultant for: AstraZeneca Pharmaceuticals LP
    Served as a speaker or a member of a speakers bureau for: Clovis Oncology; Merck & Co., Inc.; TESARO, Inc.


  • Lisa Brauer, PhD

    Scientific Director, Medscape, LLC


    Disclosure: Lisa Brauer, PhD, has disclosed no relevant financial relationships.

  • Andrew D. Bowser, ELS, CHCP

    Scientific Director, Medscape, LLC


    Disclosure: Andrew D. Bowser, ELS, CHCP, has disclosed the following relevant financial relationships:
    Spouse served as a speaker for Shire and as an advisor or consultant for ALK, CSL Behring, and Pharming.

CME Reviewer

  • Amy Bernard, MS, BSN, RN-BC, CHCP

    Lead Nurse Planner, Medscape, LLC


    Disclosure: Amy Bernard, MS, BSN, RN-BC, CHCP, has disclosed no relevant financial relationships.

Peer Reviewer

This activity has been peer reviewed and the reviewer has disclosed no relevant financial relationships.

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Maintenance Therapy for Ovarian Cancer: Practical Considerations for Community Practice


  • Maintenance Therapy for Ovarian Cancer: Practical Considerations for Community Practice

    • Slide 1.

      Slide 1.

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    • Best Practices for Maintenance Therapy in Recurrent Ovarian Cancer

      • Slide 3.

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      • Overview of Maintenance Therapy for Recurrent Ovarian Cancer[1]

        • Slide 4.

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        • Overview of Maintenance Therapy for Recurrent Ovarian Cancer (cont)[1-4]

          • The niraparib and rucaparib studies enrolled all comers (ie, BRCA and non-BRCA mutated cancers)

        • Slide 5.

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        • Overview of Maintenance Therapy for Recurrent Ovarian Cancer (cont)[1-7]

          • Slide 6.

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          • Maintenance Strategies for Platinum-Sensitive Recurrent Ovarian Cancer[2-7]

            • There are inherent differences in how maintenance is defined in the context of poly (ADP-ribose) polymerase (PARP) inhibitor therapy and bevacizumab therapy
              • PARP maintenance is added at the end of chemotherapy (not concomitantly) to avoid overlapping bone marrow suppression
              • Bevacizumab maintenance therapy trials have looked at chemotherapy alone versus chemotherapy-bevacizumab combined followed by bevacizumab maintenance
            • This can make it challenging for patients to discern between regimens and maintenance approaches

          • Slide 7.

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          • Important Differences Between PARP Inhibitor and BEV Maintenance Trials[2-7]

            • Slide 8.

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            • BEV Maintenance Studies[6,7]

              • OCEANS showed a progression-free survival (PFS) improvement of about 4 months for added bevacizumab, with no difference in overall survival
              • GOG-0213 also showed a PFS improvement approaching 4 months, and overall survival that was trending toward significance or just reaching significance, depending on analysis

            • Slide 9.

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            • The OCEANS Trial[6]

              • OCEANS trial: all subgroups examined showed improvement in PFS

            • Slide 10.

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            • The OCEANS Trial (cont)[6]

              • However, overall survival really was not improved with bevacizumab added

            • Slide 11.

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            • The GOG213 Trial[7]

              • Neither prior bevacizumab nor the treatment-free interval influenced outcomes on bevacizumab

            • Slide 12.

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            • BEV-Related Toxicities in BEV Maintenance Trials[6,7]

              • Significant adverse events were more frequent when bevacizumab was added to chemotherapy

            • Slide 13.

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            • Additional Lower Grade Toxicities of BEV in the OCEANS Trial[6]

              • Additional lower-grade toxicities are present with bevacizumab, including arthralgias, cough, dysphonia, and epistaxis

            • Slide 14.

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            • Biochemical Properties of PARP Inhibitors[14-16]

              • The 3 PARP inhibitors that are now FDA-approved in ovarian cancer have different half-lives and different biochemical structures as well

            • Slide 17.

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            • Predictors of Response to PARP Inhibitors: Number of Prior Lines of Therapy and Platinum Sensitivity[18]

              • Overall response rates declined with increasing platinum resistance and more lines of treatment

            • Slide 20.

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            • Randomized Trial of Maintenance Olaparib in Platinum-Sensitive High-Grade Serous Relapsed Ovarian Cancer - Study 19: Design[1]

              • Study 19 was a seminal study in this area

            • Slide 21.

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            • Study 19: PFS[1,19]

              • The median PFS in the overall population was approximately 4 months, but in a retrospective subgroup analysis looking at BRCA-mutated cancers, there was a more than 7-month improvement

            • Slide 22.

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            • SOLO2/ENGOT-OV21:Study Design[3]

              • SOLO2 included only patients whose cancers have an underlying BRCA mutation

            • Slide 23.

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            • SOLO2/ENGOT-OV21:PFS in BRCA-Mutated, Platinum-Sensitive Disease[3]

              • Slide 24.

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              • Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer[2]

                • Slide 25.

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                • ENGOT-OV16/NOVA: Primary Analysis of PFS in Patient Subsets[2]

                  • In the 3 primary efficacy populations, median PFS is significantly prolonged with niraparib vs placebo
                  • For the germline BRCA-positive patients, median PFS was 5.5 months in the placebo arm, similar to what was seen in the SOLO2 trial

                • Slide 27.

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                • ENGOT-OV16/NOVA: Niraparib Effect on PFS in Patients Without Germline BRCAm Most Notable in HRD-Positive Subset[2]

                  • Subgroup populations also showed improvement in PFS albeit to a lesser degree compared with the initial populations

                • Slide 28.

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                • ARIEL3: Investigator-Assessed PFS[4]

                  • In all 3 subgroups the addition of rucaparib vs placebo at maintenance generated an improvement in median PFS
                  • As in previous studies, the BRCA-mutated groups appeared to derive the most benefit from a PARP inhibitor
                  • Median PFS of 5.4 months in the placebo group (BRCA mutant) was again quite similar to both SOLO2 and NOVA trials previously described

                • Slide 31.

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                • Summary of Phase 3 PARP Maintenance Studies[20]

                  • Given that the 3 available agents show comparable efficacy, treatment selection is based on the characteristics other than efficacy

                • Slide 32.

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                • PARP Inhibitor Characteristics Inform Treatment Choices

                  • Slide 33.

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                  • Challenge: Price of PARP Inhibitors[21]

                    • These PARP inhibitors have fairly similar cost per month (US$)
                    • Patient copays may be substantial
                    • Specific initiatives (eg, patient-assistance programs) may bring down the cost of PARP inhibitors

                  • Slide 34.

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                  • Special Considerations for Maintenance Therapy in Community Practice

                    • Slide 36.

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                    • BRCA Mutations and Cancer Risk[29]

                      • Risk of cancers among women with BRCA1/2 mutations is considerably elevated compared to the general population

                    • Slide 39.

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                    • NCCN Testing Guideline[30]

                      • While all women with ovarian cancer should be tested, unfortunately some patients are still falling through the cracks
                      • Some providers are still relying on older ideas that perhaps age and family history should be considered in the decision of whether or not to test

                    • Slide 40.

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                    • Limitations to Multigene Testing

                      • Slide 43.

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                      • Genetic Testing: Somatic Testing[32]

                        • Strategies for somatic testing have been debated
                        • Start with somatic testing may have financial advantages, but there is some lingering concern that some mutations could be missed

                      • Slide 45.

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                      • SOLO1: Olaparib Phase 3 Trial First-Line Maintenance Study, in Collaboration With the GOG - Study GOG 3004[34]

                        • Slide 48.

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                        • SOLO1: Investigator-Assessed PFS[34]

                          • PFS advantage was impressive and plateaued despite drug discontinuation
                          • Median PFS of only 13.8 months was observed in the placebo arm; some expected it would be longer

                        • Slide 49.

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                        • SOLO1: Investigator-Assessed PFS Subgroup Analysis[34]

                          • All subgroups had improvement in their PFS favoring olaparib

                        • Slide 50.

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                        • SOLO1: Most Common Grade 3/4 Toxicities[34]

                          • Toxicities in this trial are very similar to the toxicities in the recurrent setting
                          • The most common included gastrointestinal (GI) toxicities, bone marrow suppression and fatigue
                          • A fair number of patients in the placebo arms also experienced toxicities
                          • In general, patients did not have to come off of trial related to the toxicities

                        • Slide 51.

                          Slide 51.

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                        • Key Grade 3/4 Toxicities From Phase 3 Maintenance Studies[2-4]

                          • Toxicities from maintenance studies show a very similar theme involving bone marrow suppression with anemia and thrombocytopenia, as well as GI toxicities including nausea and also fatigue
                          • Hypertension is a toxicity that was described in patients on niraparib
                          • There were some elevations in liver function tests (LFTs) described in the ARIEL3 trial for patients on rucaparib

                        • Slide 52.

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                        • Practical Considerations With PARP Inhibitors[16,15,14]

                          • There are some of the practical considerations that maybe can help you to decide which PARP would be appropriate for a particular patient,
                          • Both rucaparib and olaparib are metabolized via the CYP enzymes, whereas niraparib is metabolized via carboxyl esterases.
                          • Rucaparib has not had any important described drug-drug interactions, so there is no need to make any dose modifications or take patients off of other medications
                          • For olaparib, might need to consider reducing the dosage if patients are on concurrent strong or moderate CYP3A inhibitors
                          • Rucaparib and olaparib can interfere with renal transport creatinine proteins; niraparib does not have that same impact, so elevation in creatinine should not be seen

                        • Slide 53.

                          Slide 53.

                          (Enlarge Slide)
                        • PARP Inhibitor Toxicity: Bone Marrow Suppression[16,15,14,36]

                          • It is very important to allow your patients to have time to recover from their toxicities before you try to start them on PARP inhibitor maintenance
                          • This may help to lessen and mitigate some of the potential toxicities

                        • Slide 54.

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                        • Niraparib Dose Level by Month on Treatment[2,37,33]

                          • Many patients did require dose-modifications on the NOVA trial related to toxicities
                          • The most common dose after patients had been on treatment for a prolonged period was 200 mg

                        • Slide 55.

                          Slide 55.

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                        • NOVA: Integrated Analysis to Predict Which Patients Are at Risk for Grade 3/4 Thrombocytopenia[2,37,33]

                          • Investigators sought variables which were predictive of experiencing significant levels of thrombocytopenia
                          • Two identified as important were weight and baseline platelet count
                          • Patients who have those parameters might be considered for starting at a lower dose (eg, 200 mg/day)

                        • Slide 56.

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                        • Dose Modifications Result in Decreased Incidence of AEs[2,33]

                          • Patients who had required dose reductions were able to continue on the trial and were able to tolerate the medications

                        • Slide 57.

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                        • Estimated Probability of PFS by Dose Level After Month 3[33]

                          • Slide 58.

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                          • PARP Inhibitor Toxicity: Fatigue

                            • Slide 60.

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                            • PARP Inhibitory Toxicity: Elevated LFTs[4,16]

                              • In general, there was a short, limited increase in LFTs which did improve over time
                              • This did not require dose modification or dose delay, and was not associated with liver dysfunction

                            • Slide 62.

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                            • PARP Inhibitors: Practical Implications

                              • Slide 66.

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                              • Patients as Self-Advocates[41]

                                • Patients are becoming their own advocates, and they are often helped on this by a toolkit developed by the National Coalition of Cancer Survivorship (NCCS), the oldest cancer survival advocacy organization in the United States
                                • The toolkit teaches patients the skills they need to be more proactive in our own medical care

                              • Slide 69.

                                Slide 69.

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                              • SHARE Cancer Support:[42]

                                • The smoothest journeys of all ovarian cancer patients are the ones that include peer-support
                                • Every ovarian cancer survivor can have unparalleled peer-support from the SHARE organization which serves both breast cancer and ovarian cancer survivors
                                • SHARE is a free, non-profit nation-wide support organization which operates a phone hotline for ovarian cancer patients staffed by ovarian cancer survivors

                              • Slide 70.

                                Slide 70.

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                              • Effective Communication

                                • It is imperative that patients know the clearest communication pathway from the doctor to the patient (ie, portal, secure email, phone call)
                                • In the era of the 5-minute doctor visit, it is helpful to the patient if there is a team approach at the doctor's office, starting with the receptionist, and including office staff, nurses, and others who will spend more time with her than the doctor will be able to

                              • Slide 71.

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                              • To Be Continued

                                • Women may need "dialogue reframing" to help see themselves as someone other than an ovarian cancer victim, but rather, a survivor
                                • A 5-minute conversation about ovarian cancer as a chronic disease can completely change a patent's attitude
                                • The fact that a highly-trained professional explains what it means to have a chronic disease is very meaningful and empowering to the patient

                              • Slide 72.

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                              • This content has been condensed for improved clarity.


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