Veliparib in Ovarian Cancer: Final OS & Symptoms Results

Original research
Veliparib concomitant with rst-line chemotherapy and as maintenance
therapy in ovarian cancer: Final overall survival and disease-related
symptoms results
Robert L. Coleman
a,*
, Gini F. Fleming
b
, Mark F. Brady
c
, Elizabeth M. Swisher
d
,
Karina D. Steffensen
e
, Michael Friedlander
f
, Aikou Okamoto
g
, Kathleen N. Moore
h
,
Charles A. Leath III
i
, David Cella
j
, Zhaowen Sun
k
, Shilpen Patel
k
, Zequn Tang
k
,
Christine K. Ratajczak
k
, Carol Aghajanian
l
, Michael A. Bookman
m
a
Texas Oncology, US Oncology Network, Shenandoah, TX, USA
b
University of Chicago Medicine, Chicago, IL, USA
c
NRG Oncology Statistics and Data Management Center, Roswell Park Cancer Institute, Buffalo, NY, USA
d
University of Washington and Fred Hutchinson Cancer Center, Seattle, WA, USA
e
Center for Shared Decision Making, Vejle/Lillebaelt Hospital of Southern Denmark, Vejle, Denmark
f
Prince of Wales Clinical School, University of New South Wales and Royal Hospital for Women, Randwick, NSW, Australia
g
Jikei University School of Medicine, Tokyo, Japan
h
Stephenson Cancer Center at the University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
i
O’Neal Comprehensive Cancer Center at the University of Alabama at Birmingham, Birmingham, AL, USA
j
Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL, USA
k
AbbVie, Inc., North Chicago, IL, USA
l
Memorial Sloan Kettering Cancer Center, New York, NY, USA
m
Kaiser Permanente Northern California, San Francisco, CA, USA
ARTICLE INFO
Keywords:
Veliparib
PARP inhibitor
Ovarian cancer
Overall survival
Maintenance
Phase 3 trial
ABSTRACT
Introduction: In the VELIA trial, the addition of veliparib to standard rst-line platinum-based chemotherapy and
continued as maintenance resulted in signicantly longer median progression-free survival (PFS) compared with
carboplatin plus paclitaxel induction therapy alone (23.5 vs 17.3 months; p <0.001) in patients with ovarian
cancer. We now report nal overall survival (OS) and updated safety and disease-related symptoms (DRS) from
patient-reported outcomes of the trial.
Methods: This randomized, placebo-controlled, double-blind, multicenter, phase 3 study enrolled adult women
with an initial diagnosis of stage III/IV high-grade serous ovarian cancer undergoing primary or interval cyto-
reductive surgery. Patients were randomized 1:1:1 to chemotherapy plus veliparib followed by veliparib
maintenance (veliparib-throughout), chemotherapy plus veliparib followed by placebo maintenance (veliparib-
combination-only), or chemotherapy plus placebo followed by placebo maintenance (placebo-throughout). PFS
was the primary endpoint; OS and DRS were secondary endpoints.
Results: In the intention-to-treat population (N =1140), median OS was 59.2 months (95 % condence interval:
52.1, 68.2) for the veliparib-throughout group, 58.0 (50.6, 64.1) months for veliparib-combination-only, and
57.8 (52.3, 63.8) months for placebo-throughout. OS outcomes were not signicantly different between arms
overall or in the BRCA-decient and homologous recombination-decient cohorts. No new safety signals were
identied during the longer follow-up period and DRS analyses indicated there was no signicant additional
symptom-related burden overall when veliparib was added to chemotherapy or used for maintenance.
Conclusion: No OS or DRS benet of addition of veliparib to platinum-based chemotherapy and continued as
maintenance therapy was detected in this study, despite an observed benet over chemotherapy alone in PFS.
* Corresponding author.
E-mail address: [email protected] (R.L. Coleman).
Contents lists available at ScienceDirect
European Journal of Cancer
journal homepage: www.ejcancer.com
https://doi.org/10.1016/j.ejca.2025.115587
European Journal of Cancer 225 (2025) 115587
Available online 17 June 2025
0959-8049/© 2025 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

1. Introduction
The treatment landscape for ovarian cancer has signicantly evolved
with the development of poly(ADP-ribose) polymerase (PARP) in-
hibitors; however, the most effective treatment regimen and target pa-
tient population remain to be identied. PARP inhibitors have shown
efcacy as monotherapy, in combination regimens, and as maintenance
treatment after response to platinum-based chemotherapy [1−4].
Combining PARP inhibition with platinum-based chemotherapy can
enhance the antitumor cytotoxic effect, but may also result in increased
hematologic toxicity requiring reduced and/or intermittent dosing
[5−7], making this strategy challenging. US Food and Drug Adminis-
tration and European Medicines Agency-approved regimens for PARP
inhibition rely on the use of PARP inhibitors in a post-chemotherapy
maintenance phase, and have resulted in extended progression-free
survival (PFS) [2,8]. In the SOLO-1 study, maintenance olaparib
improved overall survival (OS) in patients with BRCA-mutated ovarian
cancer, though not statistically signicant at the interim analysis [9].
Veliparib is a potent and selective PARP-1 and PARP-2 inhibitor with
good oral bioavailability [10] and can be safely administrated with
platinum-based chemotherapy at a reduced dose. The international,
phase 3, placebo-controlled VELIA trial (NCT02470585; GOG-3005)
investigated the addition of veliparib to standard platinum-based
chemotherapy (carboplatin and paclitaxel) and continued as mainte-
nance therapy [11]. Induction therapy with carboplatin, paclitaxel, and
veliparib followed by veliparib maintenance signicantly prolonged
median PFS (23.5 months) compared with carboplatin plus paclitaxel
induction therapy alone (17.3 months, hazard ratio [HR] 0.68; 95 %
condence interval [CI]: 0.56, 0.83; p <0.001) after a median follow-up
of 28 months. Among patients with BRCA-mutated tumors, median PFS
was 34.7 months with veliparib induction and maintenance compared
with 22.0 months without veliparib (HR 0.44; 95 % CI: 0.28, 0.68;
p <0.001), and among patients with homologous
recombination-decient (HRD; included BRCA-decient) tumors, me-
dian PFS was 31.9 months with veliparib induction and maintenance
compared with 20.5 months without veliparib (HR 0.57; 95 % CI: 0.43,
0.76; p <0.001). While adding veliparib to chemotherapy increased the
incidence of anemia and thrombocytopenia, quality of life did not
appear to be negatively affected. At the time of the primary analysis, OS
data were not sufciently mature. Herein, we present the nal OS
analysis, as well as updated safety and disease-related symptoms from
patient-reported outcomes of the study.
2. Methods
2.1. Study design
This randomized, placebo-controlled, double-blind, multicenter,
phase 3 study investigated veliparib in combination with carboplatin
and paclitaxel and as continuation maintenance therapy in patients with
ovarian cancer. The complete trial design, eligibility criteria, assess-
ments, and statistical analysis were published previously [11]. Briey,
adult women (≥18 years) with an initial diagnosis of stage III/IV
high-grade serous ovarian cancer who were treated with primary or
interval cytoreductive surgery were enrolled. Patients were stratied by
disease stage (III vs IV), residual disease and choice of regimen, region of
the world (Japan vs North America vs rest of world), and germline BRCA
(gBRCA) mutation status (gBRCA positive vs gBRCA negative or un-
known) and then randomized 1:1:1 to receive chemotherapy plus veli-
parib followed by veliparib maintenance (veliparib-throughout group),
chemotherapy plus veliparib followed by placebo maintenance (veli-
parib-combination-only group), or chemotherapy plus placebo followed
by placebo maintenance (placebo-throughout group). The HRD popu-
lation was dened as all patients in the BRCA-decient population as
well as those with HRD tumors based on HRD score as determined using
centralized testing. The BRCA-decient population was dened as
patients who had deleterious or suspected deleterious germline or
tissue-based mutations. The gBRCA status of each patient was deter-
mined by the sponsor core laboratory.
During chemotherapy, patients received 150 mg oral veliparib or
matching placebo twice daily, and during maintenance patients received
single-agent veliparib at a dose of 300 mg or matching placebo twice
daily for 2 weeks and then 400 mg or matching placebo twice daily up to
30 additional 21-day cycles (90 weeks), for a total trial regimen of 36
cycles (108 weeks). After the maintenance phase ended, patients entered
a long-term follow-up phase, during which standard-of-care, disease-
related symptoms, and tumor assessments continued. The primary ef-
cacy endpoint for the study was PFS; secondary endpoints were OS and
disease-related symptoms as measured by National Comprehensive
Cancer Network/Functional Assessment of Cancer Therapy Ovarian
Symptom Index (NFOSI) scores. The study was approved by institutional
review boards at the investigational sites. All patients provided written
informed consent.
2.2. Assessments
OS was dened as days from randomization to death, regardless of
cause, and was estimated for each treatment arm using Kaplan-Meier
methodology. Estimated median OS times with 95 % CI are presented.
For comparison between treatment arms (veliparib-throughout group vs
placebo-throughout group; veliparib-combination-only group vs
placebo-throughout group), a stratied log-rank test was applied. OS
analysis was performed for the whole population, as well as BRCA-
decient and HRD subgroups. Per protocol, the number of events needed
to have 80 % power to detect a statistically signicant treatment effect
for the nal OS analysis was at least 350, 166, and 79 deaths for each
pairwise treatment group comparison made in the whole, HRD, and
BRCA-decient populations, respectively. Due to early study closure, the
target number of events was not reached in the veliparib-throughout
group vs the placebo-throughout group in the BRCA population.
Adverse events were categorized per Medical Dictionary for Regu-
latory Activities v21.1, and graded according to the National Cancer
Institute Common Terminology Criteria for Adverse Events v4.03. All
patients who received at least one dose of veliparib or placebo were
included in the safety analyses.
The Disease-Related Symptoms score is a nine-item subset of the
NFOSI-18 questionnaire. The nine items encompass (lack of) energy,
pain, feeling ill, cramps/swelling in the stomach area, fatigue, con-
stipation, bowel control, insomnia, and worry about worsening condi-
tion [12]. The questionnaire was administered every 3 months until
disease progression or up to 2 years after receipt of the rst dose,
whichever was later. Scores range from 0–36 (higher scores indicate
lower symptom burden) and a three-point group difference was
considered clinically meaningful.
3. Results
3.1. Patients
A total of 1140 patients were randomized and 1124 received at least
one dose of study treatment. Of those who received study treatment, 298
were included in the BRCA-decient cohort and 627 in the HRD cohort.
Patient characteristics were comparable in the three treatment arms
(Table 1). Median exposure to veliparib or placebo was 324 days (range
1–840) in the veliparib-throughout group, 370.5 (1–827) days in the
veliparib-combination-only group, and 391 (1–833) days in the placebo-
throughout group. At the time of this analysis, all patients had dis-
continued treatment.
3.2. Efcacy
For this nal analysis, the median follow-up time was 81.1 months
R.L. Coleman et al.
European Journal of Cancer 225 (2025) 115587
2

(range 0.03–96.9) in the veliparib-throughout group, 81.2 (0.03–97.6)
months in the veliparib-combination-only group, and 81.7 (0.16–96.7)
months in the placebo-throughout group. The total number of deaths in
each treatment group for the whole population and the BRCA-decient
and HRD subgroups are presented in Figure 1. The median OS in the
total population was 59.2 months (95 % CI: 52.1, 68.2) for the veliparib-
throughout group, 58.0 (50.6, 64.1) months for the veliparib-
combination-only group, and 57.8 (52.3, 63.8) months for the
placebo-throughout group. OS outcomes were not signicantly different
when comparing veliparib-throughout to placebo-throughout (p =0.28)
or veliparib-combination-only to placebo-throughout (p =0.64)
(Figure 1A). Similar results were seen in the BRCA-decient cohort and
the HRD cohort (Figure 1B–C). Comparing OS analyses in subgroups
dened according to potential prognostic factors also demonstrated no
signicant differences between the veliparib-throughout and placebo-
throughout groups (Figure 2).
3.3. Safety
Table 2 presents an overview of the safety outcomes. All patients
experienced treatment-emergent adverse events (TEAEs). The most
common any-grade TEAEs (≥65 % of patients) were nausea (80 % in
veliparib-throughout group, 72 % in veliparib-combination-only group,
67 % in placebo-throughout group), neutropenia (75 %, 75 %, 68 %),
and peripheral sensory neuropathy (64 %, 63 %, 69 %). TEAEs with a
>10 % higher frequency in the veliparib-throughout group vs the
placebo-throughout group consisted of nausea (80 % vs 67 %), throm-
bocytopenia (58 % vs 33 %), vomiting (49 % vs 36 %), and anemia
(64 % vs 53 %). The most frequently reported grade 3–4 TEAEs (≥20 %
of patients) were neutropenia (58 % in veliparib-throughout group,
62 % in veliparib-combination-only group, 50 % in placebo-throughout
group), anemia (38 %, 41 %, 26 %), and thrombocytopenia (28 %,
31 %, 8 %). Grade 3–4 TEAEs with a >10 % higher frequency in the
veliparib-throughout group vs the placebo-throughout group were
anemia (38 % vs 26 %) and thrombocytopenia (28 % vs 8 %). There was
one TEAE of myelodysplastic syndromes (MDS) that later developed into
acute myeloid leukemia. This event occurred in the veliparib-
throughout group, during the maintenance phase. In addition, there
were two non–treatment-emergent events of MDS that occurred >30
days after last study drug administration, one in the veliparib-
combination-only group and one in the veliparib-throughout group.
TEAEs resulting in discontinuation of veliparib occurred in 101
(27 %) patients in the veliparib-throughout group, while 43 (12 %)
patients discontinued placebo in the placebo-throughout group. Dose
interruption (69 % vs 48 %) or reduction (24 % vs 6 %) of veliparib or
placebo was also more common in the veliparib-throughout group
compared with the placebo-throughout group. TEAEs leading to death
occurred in eight patients in the veliparib-throughout group, seven pa-
tients in the veliparib-combination-only group, and six patients in the
placebo-throughout group. Most deaths were assessed as unrelated to
veliparib or placebo; one event of septic shock was considered related to
veliparib in the veliparib-combination-only group.
3.4. Disease-related symptoms scores
The mean baseline Disease-Related Symptoms score was similar
between treatment arms, ranging from 24.3 to 25.3. The change in
Disease-Related Symptoms score from baseline was not signicantly
different between the veliparib-throughout or veliparib-combination-
only group compared with the placebo-throughout group for any
treatment cycle, indicating no signicant additional symptom-related
burden with the addition of veliparib to chemotherapy and with
continuing veliparib as maintenance treatment overall. The Disease-
Related Symptoms score of patients who remained on treatment
improved from cycle 3 to cycle 11 in all treatment arms and then
remained relatively stable until cycle 35 (Figure 3).
4. Discussion
The primary analysis of the VELIA trial demonstrated signicant
improvements in PFS for the veliparib-throughout arm in all three
analyzed cohorts (intent-to-treat population, BRCA-decient cohort,
and HRD cohort) [11]. In the current report, focusing on OS, no
improvement in median OS was observed with the addition of veliparib
to chemotherapy and its continuation as maintenance treatment. Sub-
group analysis did not identify specic patient populations with
increased survival benet of the veliparib-throughout regimen. A similar
outcome with veliparib was seen in the BROCADE3 study, where addi-
tion of veliparib to carboplatin and paclitaxel was evaluated in patients
with breast cancer. The primary analysis of that trial found a signicant
improvement in PFS [13], which did not translate to an OS benet in the
nal analysis [14].
This lack of congruency between PFS and OS has been seen in mul-
tiple trials in primary and recurrent ovarian cancer [2,8,9,15−17], and a
number of factors may be involved. Some trials allow patients in the
control group to cross over to the experimental treatment upon
Table 1
Patient demographics and baseline characteristics.
Placebo-
throughout
group(N¼375)
Veliparib-
combination-
only group
(N¼383)
Veliparib-
throughout
group(N¼382)
Median age, years
(range)
62 (33–86) 62 (22–88) 62 (30–85)
Geographic region   
North America 266 (71) 261 (68) 267 (70)
Other 109 (29) 122 (32) 115 (30)
ECOG performance
status, n (%)
0 226 (60) 210 (55) 224 (59)
1 138 (37) 157 (41) 141 (37)
2 7 (2) 9 (2) 12 (3)
Missing 4 (1) 7 (2) 5 (1)
Stage of disease, n (%)   
III 292 (78) 288 (75) 295 (77)
IV 82 (22) 94 (25) 87 (23)
Missing 1 (0.3) 1 (0.3) 0
BRCA mutation
status, n (%)
Deleterious
mutation
92 (25) 98 (26) 108 (28)
No deleterious
mutation
254 (68) 243 (63) 245 (64)
Missing 29 (8) 42 (11) 29 (8)
Homologous
recombination
deciency, n (%)
Yes 207 (55) 206 (54) 214 (57)
No 124 (33) 123 (32) 125 (33)
Missing 44 (12) 54 (14) 43 (11)
Surgery, n (%)   
Primary 250 (67) 253 (66) 261 (68)
Interval 107 (29) 114 (30) 99 (26)
None 18 (5) 16 (4) 22 (6)
Macroscopic residual
disease after
primary/interval
surgery, n (%)
Yes 107 (29) 123 (32) 110 (29)
No 246 (66) 240 (63) 247 (65)
Missing 4 (1) 4 (1) 3 (1)
Paclitaxel regimen, n
(%)
Weekly 193 (51) 203 (53) 190 (50)
Every 3 weeks 179 (48) 178 (46) 189 (49)
Missing 3 (1) 2 (1) 3 (1)
ECOG, Eastern Cooperative Oncology Group.
R.L. Coleman et al.
European Journal of Cancer 225 (2025) 115587
3

progression, which can reduce differences in OS between groups, even if
there was a clear difference in PFS. There is often a long postprogression
survival period in ovarian cancer trials, during which patients usually
receive multiple lines of cancer therapy, including other PARP
inhibitors. In the current study, any posttreatment PARP inhibitor
therapy was received by 19 % of patients in the veliparib-throughout
group, 30 % of patients in the veliparib-combination-only group, and
33 % of patients in the placebo-throughout group. Aside from imbalance
Fig. 1. Kaplan-Meier estimates of overall survival in the (A) total, (B) BRCA-decient, and (C) HRD population. HRD, homologous recombination-decient.
R.L. Coleman et al.
European Journal of Cancer 225 (2025) 115587
4

between the original treatment arms, new or experimental agents can
become available during the survival follow-up period and impact the
OS data. Due to the relatively long postprogression survival period in
VELIA, most patients (74.9 % in placebo-throughout group, 75.7 % in
veliparib-combination-only group, 66.9 % in veliparib-throughout
group) received several lines of postprogression non-PARP inhibitor
cancer therapy as well. There may also be an impact of prior treatment
on subsequent treatment. For example, patients with recurrent ovarian
Fig. 2. Subgroup analysis of overall survival. CI, condence interval; ECOG, Eastern Cooperative Oncology Group; HR, hazard ratio; HRD, homologous
recombination decient; Q, every.
Table 2
Safety overview.
Placebo-throughout group
(N¼371)
Veliparib-combination-only group
(N¼376)
Veliparib-throughout group
(N¼377)
All grade Grade 3–4 All grade Grade 3–4 All grade Grade 3–4
TEAE occurring in ≥30% in any treatment arm, n (%) 
Any TEAE 371 (100) 287 (77) 376 (100) 330 (88) 377 (100) 332 (88)
Nausea 250 (67) 10 (3) 269 (72) 15 (4) 302 (80) 31 (8)
Neutropenia 253 (68) 184 (50) 282 (75) 234 (62) 284 (75) 217 (58)
Peripheral sensory neuropathy 256 (69) 9 (2) 235 (63) 7 (2) 241 (64) 9 (2)
Fatigue 221 (60) 12 (3) 235 (63) 18 (5) 259 (69) 32 (8)
Anemia 195 (53) 97 (26) 245 (65) 155 (41) 240 (64) 144 (38)
Alopecia 214 (58) 2 (1) 216 (57) 0 197 (52) 0
Thrombocytopenia 122 (33) 30 (8) 225 (60) 115 (31) 219 (58) 105 (28)
Constipation 160 (43) 2 (1) 181 (48) 7 (2) 166 (44) 2 (1)
Diarrhea 151 (41) 9 (2) 141 (38) 11 (3) 166 (44) 8 (2)
Vomiting 133 (36) 9 (2) 133 (35) 14 (4) 186 (49) 15 (4)
Arthralgia 136 (37) 4 (1) 112 (30) 1 (0.3) 113 (30) 5 (1)
Abdominal pain 119 (32) 14 (4) 114 (30) 13 (3) 127 (34) 17 (5)
Insomnia 89 (24) 0 120 (32) 1 (0.3) 109 (29) 3 (1)
Leukopenia 89 (24) 34 (9) 88 (23) 45 (12) 113 (30) 66 (18)
TEAE leading to, n (%)   
Discontinuation of veliparib/placebo 43 (12) 50 (13) 101 (27)
Interruption of veliparib/placebo 177 (48) 230 (61) 260 (69)
Reduction of veliparib/placebo 22 (6) 18 (5) 89 (24)
Deaths, n (%)   
Occurring ≤30 days after last dose 6 (2) 7 (2) 8 (2)
Occurring >30 days after last dose 221 (60) 224 (60) 198 (53)
TEAE, treatment-emergent adverse event.
a
Reported as any-grade in ≥30% in any treatment arm.
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European Journal of Cancer 225 (2025) 115587
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