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Targeted and Immune Cancer Therapy

Advances in Ovarian Cancer Care and Unmet Treatment Needs for Patients With Platinum ResistanceA Narrative Review

To identify the key insights or developments described in this article

1 Credit CME

JAMA Oncology

Published Online: April 20, 2023

Review

Article Information and Disclosures

Debra L. Richardson, MD¹;

Ramez N. Eskander, MD²;

David M. O’Malley, MD³

Author Affiliations

¹Division of Gynecologic Oncology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City
²Department of Obstetrics, Gynecology and Reproductive Sciences, Division of Gynecologic Oncology, University of California San Diego Moores Cancer Center, UC San Diego Health, La Jolla
³Division of Gynecologic Oncology, The Ohio State University Wexner Medical Center and The James Comprehensive Cancer Center, Columbus

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Abstract

Importance Platinum-based chemotherapy has been the standard of care for ovarian cancer for the past 3 decades. Although most patients respond to platinum-based treatment, emergence of platinum resistance in recurrent ovarian cancer is inevitable during the disease course. Outcomes for patients with platinum-resistant ovarian cancer are poor, and options remain limited, highlighting a substantial unmet need for new treatment options.

Observations This review summarizes the current and evolving treatment landscape for platinum-resistant ovarian cancer with a focus on the development of novel compounds. Biologic and targeted therapies such as bevacizumab and poly (ADP-ribose) polymerase (PARP) inhibitors—originally approved in the platinum-resistant setting but since withdrawn—are now used in the up-front or platinum-sensitive setting, prolonging the duration of platinum sensitivity and delaying the use of nonplatinum options. The greater use of maintenance therapy and the emphasis on using platinum beyond first-line treatment has most likely been associated with a greater number of lines of platinum therapy before a patient is designated as having platinum-resistant ovarian cancer. In this contemporary setting, recent trials in platinum-resistant ovarian cancer have mostly had negative outcomes, with none having a clinically significant effect on progression-free or overall survival since the approval of bevacizumab in combination with chemotherapy. Nonetheless, a multitude of new therapies are under evaluation; preliminary results are encouraging. A focus on biomarker-directed treatment and patient selection may provide greater success in identifying novel therapies for treating platinum-resistant ovarian cancer.

Conclusions and Relevance Although many clinical trials in platinum-resistant ovarian cancer have had negative outcomes, these failures provide insights into how clinical trial design, biomarker-directed therapy, and patient selection could facilitate future successes in platinum-resistant ovarian cancer treatment.

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Article Information

Accepted for Publication: December 13, 2022.

Published Online: April 20, 2023. doi:10.1001/jamaoncol.2023.0197

Corresponding Author: Debra Richardson, MD, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, 800 NE 10th St, Oklahoma City, OK 73104 (debra-richardson@ouhsc.edu).

Conflict of Interest Disclosures: Dr Richardson reported consultancy/advisory fees from Mersana, AstraZeneca, Genentech, GlaxoSmithKline, Immunogen, and Deciphera; institutional research support from GlaxoSmithKline, Celsion, Roche, Aravive, Shattuck, Mersana, Syros, Arch Oncology, Harpoon, Hookipa, Clovis, and Karyopharm, all outside the submitted work. Dr Eskander reported consulting and advisory fees from AstraZeneca, Clovis Oncology, Myriad, Eisai, Elevar Therapeutics, Genentech/Roche, Mersana, GSK/Tesaro, Cardiff Oncology, Merck, and Immunogen; institutional research support from AstraZeneca, NovoCure, Merck, Eisai, and Clovis Oncology; speakers’ bureau fees for AstraZeneca and Eisai, all outside the submitted work. Dr O’Malley reported consulting and advisory fees from AbbVie, Adaptimmune, Agenus, Arquer Diagnostics, Arcus Biosciences, AstraZeneca, Atossa Therapeutics, Boston Biomedical, Cardiff Oncology, Celcuity, Clovis Oncology, Corcept Therapeutics, Duality Bio, Eisai, Elevar, Exelixis, Genentech, Genelux, GlaxoSmithKline, GOG Foundation, Hoffmann-La Roche, ImmunoGen, Imvax, InterVenn Biosciences, INXMED, IOVANCE Biotherapeutics, Janssen, Jazz Pharmaceuticals, Laekna, Leap Therapeutics, Luzsana Biotechnology, Merck, Merck Sharp & Dohme, Mersana Therapeutics, Myriad, Novartis, NovoCure, OncoC4, Onconova, Regeneron, Replimune, R Pharm, Roche Diagnostics, Seagen, Sorrento, Sutro Biopharma, Tarveda Therapeutics, Toray, Trillium, Umoja, Verastem, VBL Therapeutics, Vencerx Pharma, Xencor, and Zentalis; institutional research funding from AbbVie, Advaxis, Agenus, Alkermes, Aravive, Arcus Biosciences, AstraZeneca, BeiGene, Boston Biomedical, Bristol Myers Squibb, Clovis Oncology, Deciphera Pharma, Eisai, EMD Serono, Exelixis, Genentech, Genmab, GlaxoSmithKline, GOG Foundation, Hoffmann-La Roche, ImmunoGen, Incyte, IOVANCE Biotherapeutics, Karyopharm Therapeutics, Leap Therapeutics, Ludwig Institute for Ca, Merck, Merck Sharp & Dohme, Mersana, US National Cancer Institute, Novartis, NovoCure, NRG Oncology, OncoC4, OncoQuest, Pfizer, Precision Therapeutics, Prelude Therapeutics, Regeneron Pharmaceuticals, Radiation Therapy Oncology Group, Rubius Therapeutics, Seagen, Sutro Biopharma, SWOG, Tesaro, and Verastem, outside the submitted work. No other disclosures were reported.

Funding/Support: This review was supported by Mersana Therapeutics.

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: Medical writing support was provided by Jerylin Gan, PhD, and Allison Cherry, PhD (Bio Connections, Chicago, Illinois); these contributors were compensated by Mersana.

AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
1.00 credit toward the CME [and Self-Assessment requirements] of the American Board of Surgery’s Continuous Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.