DOI: 10.1111/1471-0528.
16450
www.bjog.org
Front-line ovarian cancer maintenance therapy: PARP inhibitors
for all?
JL Berger
Department of Obstetrics, Gynecology and Reproductive Sciences, Division of Gynecologic Oncology, University of
Pittsburgh Medical Center – Magee Women’s Hospital, Pittsburgh, PA, USA
Linked article: This is a mini commentary on Q Lin et al. To view this article visit https://doi.org/10.1111/1471-0528.
16411
Poly (ADP-ribose) polymerase inhibi-
tors (PARPi) have enjoyed enormous
recent success in the treatment of
ovarian cancer, a deadly and difficult
to treat disease. In recent years, PARPi
have gained approvals as monotherapy
in BRCA-mutated ovarian cancer, as
maintenance treatment after platinum-
sensitive recurrence and, most recently,
as maintenance therapy after successful
front-line treatment. These benefits
have been largely limited to women
with germline or somatic BRCA muta-
tions or homologous-recombination
deficiency (HRD), with limited efficacy
in homologous-recombination (HR) -
proficient patients.
In this issue of BJOG, Lin et al.
(BJOG 2020; https://doi.org/10.1111/
1471-0528.16411) present a meta-anal-
ysis of the four published randomised
controlled trials evaluating PARPi as
maintenance therapy after partial or
complete response to platinum-based
chemotherapy for first-line treatment
of ovarian cancer, SOLO-1 (Moore
et al. N Engl J Med 2018;379:2495–
505), PRIMA (Gonzalez-Martin et al.
N Engl J Med 2019;381:2391–402),
PAOLA-1 (Ray-Coquard et al. N Engl
J Med 2019;381:2416–28) and
VELIA (Coleman et al. N Engl J Med
ª 2020 John Wiley & Sons Ltd.
Mini commentary
2019;381:2403–15). Their work con-
cludes that the widely accepted pro-
gression-free survival (PFS) benefit
seen in BRCA-mutated patients and
HRD patients, extends to those
patients without such favourable
molecular profiles, the HR-proficient
patients.
Their work is to be commended and
shows an outcome of interest to
physicians worldwide, but it should
be interpreted with caution. Only one
phase III randomised clinical trial has
shown a benefit for front-line mainte-
nance PARPi in the HR-proficient
population. PRIMA, published in late
2019, resulted in US Food and Drug
Administration approval of niraparib
in the USA in April 2020 for front-
line maintenance regardless of BRCA
or HRD status. The PFS benefit in
this trial, while statistically significant,
is of arguable clinical significance.
HR-proficient patients had a 2.7-
month improvement in PFS (8.1 ver-
sus 5.4 months) in the niraparib arm
compared with placebo (hazard ratio
0.68; 95% CI 0.49–0.94). The other
two trials, which include HR-profi-
cient patients, PAOLA-1 and VELIA,
failed to show a statistically signifi-
cant PFS benefit in this population of
olaparib compared with placebo
(hazard ratio 0.92; 95% CI 0.72–1.17)
of veliparib compared with placebo
(hazard ratio 0.81; 95% CI 0.6–1.09),
respectively. No trial has reported an
overall survival benefit for PARPi in
front-line maintenance to date as the
data are not yet mature.
PARPi are not without toxicities, the
most common of which are nausea,
fatigue and myelosuppression. They
also carry the rare but serious risk of
secondary haematological malignan-
cies, reported at 1–2% in most trials.
Indeed, the authors of the current
study report significantly higher G3 or
worse adverse events in the PARPi
group (65.1%) compared with placebo
(48.5%). Treatment discontinuation
rates due to adverse events ranged
from 11.5 to 20.4% for PARPi com-
pared with 2.5–6.1% for placebo in the
four trials included in this meta-analy-
sis. Although these adverse effects may
be an equitable trade-off for an 11- to
19-month improvement in PFS that
BRCA or HRD patients can expect, it
is a hard sell to HR-proficient patients
who can expect to derive only a few
additional months.
Lin et al. have indeed shown a sta-
tistical benefit for PARPi for all
1
 Mini commentary

patients in the up-front maintenance maintenance or later in treatment, Disclosure of interests

setting. Whether this benefit is mean- alone or in combination, will be the None declared. A completed disclosure
ingful for all patients is still up for focus of much needed further of interests form is available to view
discussion, and when and how research. online as supporting information. &
PARPi are best used, as front-line

2 ª 2020 John Wiley & Sons Ltd.