Elsevier

Gynecologic Oncology

Volume 142, Issue 2, August 2016, Pages 225-230
Gynecologic Oncology

Primary and acquired platinum-resistance among women with high grade serous ovarian cancer

https://doi.org/10.1016/j.ygyno.2016.05.020Get rights and content

Highlights

  • Primary (PPR) and acquired (APR) platinum-resistant patients have a poor prognosis.

  • Survival is related to the number of biologic agents received in PPR patients.

  • Stage and clinical trial participation predicts survival in APR patients.

Abstract

Objective

Women with primary platinum resistant (PPR) high grade serous ovarian cancer (HGSOC) are known to have a poor prognosis. Less is known regarding outcomes in patients with acquired platinum resistance (APR). The goal of this study was to evaluate survival in both PPR and APR patients.

Methods

A retrospective review of HGSOC patients diagnosed between 2000 and 2010 was performed. Descriptive statistics summarized clinical characteristics and demographics. The Kaplan-Meier method estimated progression free survival (PFS) and overall survival (OS). The association of OS and clinical factors was modeled using Cox proportional-hazards.

Results

Of the 330 patients identified, 81 (25%) had PPR. Of the remaining women, 55 (22%) developed APR. Median PFS of PPR patients was 4.2 months and median OS was 17.8 months. On multivariate analysis, the number of biologic agents received was the only predictor of OS. Patients with APR had a median PFS of 14.2 months and a median OS of 56 months. OS from the date of platinum resistance was 21.9 months, though this was not different than PPR patients (p = 0.19). Multivariate analysis found cancer stage and clinical trial participation to be associated with OS.

Conclusions

Platinum resistance confers a poor prognosis in the APR and PPR setting. The number of biologic agents received is the strongest predictor of OS among women with PPR. Cancer stage and clinical trial participation predicts OS in patients with APR. Providing opportunities to participate in clinical trials, especially those involving targeted therapy, should be a priority in these populations.

Introduction

Though ovarian cancer only accounts for approximately 3% of cancer cases among women, it is one of the most deadly. In 2015, it is estimated that there will be approximately 21,000 new ovarian cancer cases, and more than 14,000 women will die from the disease [1]. Though most patients will achieve remission with front-line platinum-based chemotherapy, up to 80% of these women will recur [2].

Upon relapse, ovarian cancer patients are classified according to the length of time since they last received a platinum agent. Patients who relapse within six months of completing initial platinum therapy are primary platinum-resistant. These women carry a poor prognosis, with response rates to subsequent lines of therapy ranging from 7 to 20%. Patients who relapse more than 6 months following primary platinum therapy are considered to be platinum-sensitive. In contrast to platinum-resistant patients, women who are platinum-sensitive can expect response rates of 30–90% to additional platinum agents, with higher response rates noted in patients with a longer platinum-free interval. Unfortunately, almost all platinum-sensitive patients will eventually develop resistance, at which point they are considered to have acquired platinum-resistance [3], [4], [5], [6].

The poorer prognosis of platinum-resistant ovarian cancer as compared with platinum-sensitive ovarian cancer is well-documented. However, there is no published data evaluating outcomes in the acquired platinum-resistant population. The purpose of this study is to describe survival among women with acquired platinum-resistance as compared with women with primary platinum-resistance in a cohort of patients with high grade serous ovarian cancer.

Section snippets

Materials and methods

A retrospective review was conducted of women with high grade serous ovarian cancer treated at The University of Oklahoma Health Sciences Center between January 2000 and December 2010. Approval was obtained from the Institutional Review Board (IRB) prior to initiating the study. As no data was collected prospectively, a waiver of informed consent was granted by the IRB. Women were excluded from the study if there was no histologic confirmation of their diagnosis, the status of platinum

Results

Of the 330 women included in the study, the majority presented with stage III (72.4%) or stage IV (15.8%) disease. In total, 81 (25%) women were primary platinum-resistant. Of the remaining 249 patients, 55 (22%) developed acquired platinum-resistance during the study period. Demographic and clinical characteristics of these groups are summarized in Table 1.

Discussion

Given that platinum-based chemotherapy is currently the mainstay of therapy for high-grade serous ovarian cancer, platinum-resistance is a major limitation in the management of this disease. In the present study, 25% of patients had primary platinum-resistant ovarian cancer and an additional 22% developed acquired platinum resistance during the follow-up period. There were few patients identified with acquired platinum resistance. However, this is likely due to the relatively small proportion

Potential conflicts of interest

KMM is on the advisory boards of Astra Zeneca, Immunogen, Clovis, Genentech Roche, and Merrimack. All other authors report no conflicts.

References (16)

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