Tumor burden is a potential marker of PARP inhibitor effects in ovarian cancer: a head-to-head observational series

Jing Ni,Rui Zhou,Xiaoxiang Chen,Xianzhong Cheng,Xia Xu,Wenwen Guo

doi:10.1186/s13048-020-00629-4

Abstract

BackgroundOlaparib, a poly ADP-ribose polymerase (PARP) inhibitor, has proven to be effective and safe as maintenance therapy and multiline therapy in ovarian cancer, especially in patients with BRCA mutations. This study intended to observe the influence of tumor load on the efficacy and safety of olaparib in recurrent ovarian cancer.Cases presentationThree patients harbored gBRCAwt with low tumor load (LTL), while two women harbored BRCAmt with high tumor load (HTL) were recruited. Two of the three LTL patients achieved partial response, and the other showed stable disease. Both HTL patients were assessed to have progressive disease in a short time. Olaparib appears to be effective and safe for LTL recurrent ovarian cancer patients even if it is gBRCAwt, while the response is poor in HTL patients.ConclusionsTumor load may be another potential marker to predict the effect of PARP inhibitors. The present head-to-head observational series provides new evidence on this issue for further research from bench to bedside in the future.

Highlights

Ovarian cancer is the highest mortal gynecological malignant tumor, while the five-year survival rate has long been teetering at 30% [1]
Tumor load may be another potential marker to predict the effect of poly ADP-ribose polymerase (PARP) inhibitors
PARP is essential for the repair of single-strand DNA breaks (SSDBs) in the base excision process, and PARP inhibitors (PARPi) can induce synthetic lethality in tumors with homologous recombination deficiency due to the transitions from SSDBs to double-strand DNA breaks (DSDBs) [4]

Summary

Introduction

Ovarian cancer is the highest mortal gynecological malignant tumor, while the five-year survival rate has long been teetering at 30% [1]. Clinical trials have confirmed that PARPi as first-line or second-line maintenance therapy significantly increase progression-free survival in ovarian cancer patients with a BRCA1/2 mutation [5, 6]. In addition to maintenance therapy, olaparib can be used for monotherapy of gBRCAmutated ovarian cancer after third-line chemotherapy [7].

Results

Conclusion