Ovarian Cancer Journal Scan

INTRODUCTION

In this ovarian cancer journal scan, our panel reviews:

1) The results of the randomised phase III GOG-0213 study that involved patients with platinum-sensitive, recurrent epithelial ovarian cancer, secondary surgical cytoreduction followed by chemotherapy.

2) The Food and Drug Administration approval of niraparib (ZEJULA, GlaxoSmithKline) for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy, regardless of biomarker status.

3) The randomized Phase II Trial of Nivolumab vs. Ipilimumab for Recurrent or Persistent Ovarian Cancer: An NRG Oncology Study.

Panel

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BJ Rimel, MD

Assistant Professor
Obstetrics and Gynecology
Samuel Oschin Comprehensive Cancer Institute
Cedars-Sinai Medical Center

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Brian Slomovitz, MD

Professor of Obstetrics & Gynecology
Florida International University
Gynecologic Oncologist
Broward Health

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Thomas Herzog, MD

Professor of Obstetrics and Gynecology
Deputy Director
University of Cincinnati Cancer Institute

Publications

Secondary Surgical Cytoreduction for Recurrent Ovarian Cancer
Coleman RL, et al. N Engl J Med. 2019.

Expert Review

BJ Rimel, MD

In the NEJM study from Coleman et al Nov 2019, the authors describe the analysis of GOG 213. This study was designed to provide data on the efficacy of secondary surgery to remove disease compared to another round of platinum based chemotherapy in platinum-sensitive ovarian cancer patients. Women with at least a 6 month or greater remission after their last platinum treatment who had measurable and “resectable” disease in the opinion of the treating gynecologic oncologist could be randomized. The rationale for the study was essentially to end a great debate in gynecologic oncology, “Is surgery better than chemotherapy if you can remove all the disease?” Multiple previous studies had demonstrated the importance of cytoreduction at the time of ovarian cancer diagnosis and when this study was activated in 2007, the landmark neoadjuvant chemotherapy paper by Vergote et al was 3 years away from publication.

As in in life, investigators had their own biases of how to treat these patients both implicit and explicit, leading to a 10 year time frame to accrue the necessary patients. Once the patients had been enrolled another two years of follow up elapsed before publication. Despite these challenges, this study represents the only randomized data available on surgery as a strategy for the treatment of platinum sensitive ovarian cancer.

The study results are clear that surgery did not improve overall survival for patients with a hazard ratio of 1.29 for death (95% CI, 0.97-1.72 p=0.08). Even when adjusting for platinum free interval or chemotherapy choice, the effect was exactly the same. Surgical morbidity was only 9%, which is quite low given that all the patients had prior surgery. An ad hoc exploratory analysis examining the effect of complete gross resection (R0) demonstrated that within the group who had surgery, OS and PFS were improved compared to those patients who had residual disease. However, when compared with the entire no-surgery group, there was no OS benefit (HR for death 1.03, 95% CI, 0.74 to 1.46) though the PFS benefit remained (hazard ratio for disease progression or death, 0.62; 95% CI, 0.48 to 0.80).

While it is impossible to determine from these data why the surgical arm did not perform as expected, the preplanned subgroup analysis show some clues. Serous histology, platinum free interval >12 months and treatment in the US all demonstrated significance indicating no-surgery arm (chemotherapy arm) was better. Serous ovarian cancers are more platinum sensitive as a group than other histologies but numbers were very low for the other types. Perhaps the most biologically suggestive outcome is that patients who had a platinum free interval of >12 months were strongly in the no surgery is better group. These patients most likely represent the “most sensitive” group for whom the benefit of chemotherapy cannot be overcome with surgery.

Future studies evaluating the role of surgery for recurrent ovarian cancer are ongoing (SOC-1 Trial) and these data will continue to inform the choices we make as gynecologic oncologists.

Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer
N Engl J Med . 2019 Dec 19;381(25):2391-2402.

Expert Review

Brian Slomovitz, MD

On April 29, 2020, the Food and Drug Administration approved niraparib (ZEJULA, GlaxoSmithKline) for the maintenance treatment of adult patients with advance...

Randomized Phase II Trial of Nivolumab Versus Nivolumab and Ipilimumab for Recurrent or Persistent Ovarian Cancer: An NRG Oncology Study
J Clin Oncol . 2020 Jun 1;38(16):1814-1823.

Expert Review

Thomas Herzog, MD

Background: Recurrent ovarian cancer is a challenging disease, and new therapies are needed in order to prolong women’s lives. To this end, clinicians have...