Maintenance therapy for recurrent epithelial ovarian cancer: current therapies and future perspectives \u2013 a review

Sudeep Gupta,Shona Nag,Amit Rauthan,Shyam Aggarwal,Narayanankutty Warrier

doi:10.1186/s13048-019-0579-0

Abstract

Epithelial ovarian cancer (EOC) is usually diagnosed late at an advanced stage. Though EOC initially responds to treatment, the recurrence rate is pretty high. The efficacy of different targeted therapies reduces with each recurrence. Hence there is need of effective maintenance therapy in recurrent EOC. Recently, polyADP-ribose polymerase (PARP) inhibitors (PARPi) have been approved both for initial treatment of EOC and as its maintenance treatment. PARPi have also been found to act regardless of BRCA status or homologous recombination (HR) deficiency. Several trials testing PARPi early in maintenance therapy are in progress and their results will shed light on the optimal timing of maintenance therapy that gives the most benefit with least toxicity. Right patient selection for maintenance treatment is also a challenge. Hence, though PARPi are emerging as a promising maintenance treatment in recurrent EOC with prolongation of progression free survival (PFS), results from further trials and overall survival (OS) data from current trials are awaited to fulfill the gaps in understanding the role of this pathway in treatment of EOC. This review discusses the current therapies for EOC, challenges in the treatment of recurrent EOC, recent developments and trials in recurrent EOC maintenance with special focus on PARPi and future perspectives.

Highlights

Ovarian cancer (OC) is the seventh most common malignancy diagnosed among women and eighth leading cause of cancer mortality [1]
Olaparib was granted accelerated approval based on an objective response rate (ORR) of 34% (46/137; 95% confidence interval (CI) 26–42) and median duration of response (DOR) of 7.9 months in a heavily pretreated (≥3 lines of therapy) 137 patients with advanced ovarian cancer (OC) who had a germline BRCA mutation in Study 42 [56]
The recently reported results of SOLO – 1 marks the foray of olaparib as an effective maintenance therapy in newly diagnosed germline BRCA (gBRCA) positive ovarian cancer patients who are in CR or PR to 1st line surgery and platinumbased chemotherapy

Summary

Introduction

Ovarian cancer (OC) is the seventh most common malignancy diagnosed among women and eighth leading cause of cancer mortality [1]. In patients with partially sensitive recurrent EOC, the MITO-8 trial supports the use of PBC as platinum sensitive drugs prolong PFI and improve quality of life compared to non-platinum-based therapy [30, 31].when platinum is not an option due to anaphylaxis to platinum compounds, trabectedin (MITO15 phase II trial [NCT01772979]) or PLD with trabectedin (phase 3 OVA-301 study) can be considered In these patients with anaphylaxis to platinum compound, platinum sensitive patients derived more benefit than platinum resistant patients and patients with BRCA mutation had longer PFS and OS [7, 32, 33]. Immune checkpoint inhibitors like atezolizumab are being tested in combination with bevacizumab and PBC in the ATALANTE (NCT02891824) trial [7] Both chemotherapy and non-PARPi targeted therapies (Table 1) either failed to give a conclusive benefit in EOC maintenance or the trials are still in progress with results awaited.

Primary Results endpoint

27 Postoperative PBC

Results not available