Randomized, Double-Blind, Phase III Trial Olaparib vs. Placebo Patients With Advanced FIGO Stage IIIB-IV High Grade Serious or Endometrioid Ovarian, Fallopian Tube, or Peritoneal Cancer Treated Standard First-Line Treatment

Trial ID # NCT02477644; PAOLA-1
Phase III
Drug Class DNA Damage Repair Pathway Inhibitors: PARP
Drug Name Olaparib
Alternate Drug Names AZD2281, Lynparza
Drugs in Trial Bevacizumab, Carboplatin, Olaparib, Paclitaxel
Eligible Participant

Stage III or IV, high grade serous or endometrioid, with CR or PR after first-line chemotherapy+bevacizumab

Patients Enrolled


Therapy Setting


Study Design

Double Blind, Randomized


PFS, OS, PFS2, evaluated per RECIST


Exploratory: BRCA status, HRD status


Ola (n=537) vs Placebo (n=269):

All patients:
PFS: 22.1 vs 16.6 months, H
R: 0.59 (0.49-0.72, p<0.001)
PFS2: 36.5 vs 32.6 months, HR: 0.78 (0.64-0.95, p=0.0125)
TSST: 38.2 vs 31.5 months, HR: 0.78 (0.64 -0.95, p=0.0115)
OS: 56.5 vs 51.6 months, HR: 0.92 (0.76-1.12, p=0.41)

HRD+ (incl. BRCA MUT) (n=387):
PFS: 37.2 vs 17.7 months, HR: 0.33 (0.25-0.45)
OS: 75.2 vs 57.3 months, HR: 0.62 (0.45-0.85)
OS (5 years): 65.5 vs 48.4%

Exploratory analyses:
BRCA MUT (n=237):
PFS: 37.2 vs 21.7 months, HR: 0.31 (0.20-0.47); PFS2: NR vs 45.0 months, HR: 0.53 (0.34-0.83); OS: 75.2 vs 66.9 months, HR: 0.60 (0.39-0.54)
HRD+ (excl. BRCA MUT) (n=152):
PFS: 28.1 vs 16.6 months, HR: 0.43 (0.28-0.66); PFS2: 50.3 vs 30.1 months, HR: 0.60 (0.38-0.96); OS: NR vs 52.0 months, HR: 0.71 (0.45-1.13)
non-BRCA MUT (n=569):
PFS: 18.9 vs 16.0 months,  HR: 0.71 (0.58-0.88)
HRD- (n=419):
PFS: 16.9 vs 16.0 months, HR: 0.92 (0.72-1.17); PFS2: 24.4 vs 26.4 months, HR: 1.04 (0.77-1.42); OS: 36.8 vs 40.4 months, HR: 1.19 (0.88-1.63)
Upfront surgery and no residual disease (n=245): PFS: 39.3 vs 22.1 months, HR: 0.47 (0.29-0.75)
Interval surgery and no residual disease (n=238): PFS: 22.1 vs 17.7 months, HR: 0.61 (0.41-0.91)
Upfront surgery with residual disease (n=164): PFS: 17.6 vs 13.0 months, HR: 0.74 (0.48-1.15)
Interval surgery with residual disease (n=100): PFS: 18.7 vs 12.3 months, HR: 0.70 (0.41-1.2)
Higher risk (stage III w/ upfront surgery and residual disease or who received neoadjuvant chemotherapy, or stage IV, n=596):
PFS: 20.3 vs 14.7 months, HR: 0.60 (0.49-0.79)
Higher risk and BRCA MUT: PFS: 36.0 vs 19.4 months, HR: 0.37 (0.23-0.59)
Higher risk and HRD+: PFS: 36.0 vs 16.0 months, HR: 0.39 (0.28-0.54)
Higher risk and HRD-PFS: 16.6 vs 13.9 months, HR: 0.83 (0.64-1.08)
Lower risk (stage III w/ upfront surgery and no residual disease, n=210): PFS: 39.3 vs 22.9 months, HR: 0.46 (0.30-0.72)
Lower risk and BRCA MUTPFS: NR vs 22.2 months, HR: 0.11 (0.03-0.31)
Lower risk and HRD+PFS: NR vs 22.1 months, HR: 0.15 (0.07-0.30)
Lower risk and HRD-PFS: 23.8 vs 22.9 months, HR: 1.18 (0.65-2.25)

Median time from first subsequent therapy (FST) to second subsequent therapy (SST):
Progression during Ola maint vs Progression after Ola maint vs Placebo:
Treatment with any chemo:
All patient: 6.1 vs 11.4 vs 11.9 months
HRD+: 7.2 vs 12.7 vs 13.9 months
HRD-: 6.0 vs 10.6 vs 10.8 months
Treatment with Pt-based chemo:
All patients: 7.3 vs 12.0 vs 12.9 months
HRD+: 7.3 vs 12.7 vs. 14.3 months
HRD-: 6.6 vs. 12.9 vs.11.8 months

Clinically Significant Adverse Events

Ola vs Placebo:
Serious AE: MDS, AML or aplastic anemia (1.7 vs 2.2%), hypertension (9 vs 13%), anemia (6 vs <1%)
Grade 3-4 AE: all (57 vs 51%), hypertension (19 vs 30%), anemia (17 vs 1%)


Dual maintenance therapy with olaparib and bevacizumab improves PFS and OS compared with bevacizumab maintenance alone for BRCA MUT and HRD+ patients


Ray-Coquard I et al. Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. N Engl J Med (2019) 381(25):2416-2428

Harter P et al. Efficacy of maintenance olaparib plus bevacizumab according to clinical risk in patients with newly diagnosed, advanced ovarian cancer in the phase III PAOLA-1/ENGOT-ov25 trial. Gynecol Oncol (2022) 164(2):254-264

Gonzalez-Martin A et al. Maintenance olaparib plus bevacizumab in patients with newly diagnosed advanced high-grade ovarian cancer: Main analysis of second progression-free survival in the phase III PAOLA-1/ENGOT-ov25 trial. Eur J Cancer (2022) 174:221-231

Ray-Coquard I et al. Final overall survival (OS) results from the phase III PAOLA-1/ENGOT-ov25 trial evaluating maintenance olaparib (ola) plus bevacizumab (bev) in patients (pts) with newly diagnosed advanced ovarian cancer (AOC). ESMO (2022) Abstract LBA29

Ray-Coquard I et al. Slide from presentation

Sabatier R et al. Efficacy and safety of maintenance olaparib and bevacizumab in ovarian cancer patients aged > = 65 years from the PAOLA-1/ENGOT-ov25 trial. Eur J Cancer (2023) 181:42-52

Harter P et al. Efficacy of subsequent therapies in patients (pts) with advanced ovarian cancer (AOC) in the phase III PAOLA-1/ENGOT-ov25 trial according to whether disease progression occurred during or after the end of olaparib (ola) maintenance. J Clin Oncol 41, 2023 (suppl 16; abstr 5550)

Harter P et al. Poster

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