Selection of maintenance therapy during first-line treatment of advanced ovarian cancer based on pharmacologic characteristics

ABSTRACT

Introduction

Maintenance therapy with bevacizumab and the poly (ADP-ribose) polymerase (PARP) inhibitors olaparib and niraparib after first-line treatment of advanced ovarian cancer has been approved. However, it is not clear which one should be used for which patients.

Areas covered

This paper presents a detailed analysis of data from phase 3 trials in ovarian cancer evaluating bevacizumab (ICON7, GOG-0218), olaparib (SOLO1, PAOLA-1), and niraparib (PRIMA, PRIME). We will discuss how the results of these trials relate to the ‘rebound effect,’ in which the risk of progression increases after discontinuation of bevacizumab in patients receiving bevacizumab, and to the significant difference in tissue permeability between olaparib and niraparib.

Expert opinion

In patients with homologous recombination deficiency and no macroscopic residual disease (R0) after primary debulking surgery (PDS), the combination of bevacizumab plus olaparib seems to be the best regimen. Olaparib monotherapy is suitable for patients with BRCA mutations other than PDS R0. Bevacizumab is most useful in cases with a short duration of the rebound effect, i.e. short survival. Niraparib is useful in others but may be more useful in Asians.

KEYWORDS:

• Ovarian cancer
• bevacizumab
• olaparib
• niraparib
• maintenance therapy

Article highlights

• Bevacizumab has a rebound effect after discontinuation and is effective in patients with short survival.

• Olaparib has lower tissue penetration and higher blood concentration than niraparib, but its use in combination with bevacizumab after PDS R0 increases the cure rate.

• Olaparib alone is useful in patients with BRCA mutations other than PDS R0.

• In patients with R1 surgery, IDS or non-HRD tumors, the high tissue penetration of niraparib leads to its efficacy against residual tumor cells at the end of chemotherapy.

List of abbreviations

PARP	=	poly (ADP-ribose) polymerases
R0	=	no residual disease
PDS	=	primary debulking surgery
TC	=	paclitaxel and carboplatin
EMA	=	European Medicines Agency
HRD	=	homologous recombination deficiency
HGSC	=	high-grade serous carcinoma
OS	=	overall survival
PFS	=	progression-free survival
RMST	=	Restricted Mean Survival Time
PLD	=	Liposomal doxorubicin
HR	=	DNA homologous recombination
TCGA	=	The Cancer Genome Atlas
IDS	=	interval debulking surgery
R1	=	macroscopic residual disease

Declaration of interest

N Matsumura received lecture fees from Chugai Pharmaceutical, AstraZeneca, and Takeda Pharmaceutical, as well as a research grant from AstraZeneca. N Matsumura is also an outside director of Takara Bio.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has been recruited by Research Square. Reviewers with declared or apparent competing interests are not utilized for these reviews. This reviewer was paid a small honorarium for completing the review within a specified timeframe. Honoraria for reviews such as this are paid regardless of the reviewer recommendation.

Supplementary materials

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14656566.2023.2295393

Additional information

Funding

This study was funded by the Japan Society for the Promotion of Science (JSPS) KAKENHI grant number 22K09630 (Grant-in-Aid for Scientific Research C for H Nakai).