Clinical trialPhase 3Ovarian cancer

Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer

N Engl J Med · 2019806 patients

Ray-Coquard I, Pautier P, Pignata S, Pérol D, González-Martín A, Berger R, et al. N Engl J Med. 2019. 381:2416-2428

Study type: Clinical trial
Study name: PAOLA-1 (ENGOT-ov25)
Phase: Phase 3
Design: Randomised, double-blind, international trial (2:1 ratio)
Sample size: 806 patients
Source: N Engl J Med · 2019
Trial registration: NCT02477644

In plain words

In this study, patients who had received chemotherapy together with bevacizumab were given, in addition to continuing bevacizumab, either olaparib tablets or a placebo (dummy tablet). In tumours with a DNA repair defect (HRD-positive, with or without a BRCA mutation), this combination markedly delayed the return of the disease, and after five years 65.5% of patients were alive (vs 48.4%). In HRD-negative tumours no meaningful benefit was seen, so HRD testing before deciding is important.

Key results

22.1 vs 16.6 months

Median PFS (whole population)

HR 0.59 (95% CI 0.49–0.72); P<0.001

37.2 vs 17.7 months

Median PFS in HRD-positive disease (including BRCA)

HR 0.33 (95% CI 0.25–0.45)

28.1 vs 16.6 months

Median PFS in HRD-positive disease without a BRCA mutation

HR 0.43 (95% CI 0.28–0.66)

65.5% vs 48.4%

5-year overall survival in HRD-positive disease

HR 0.62 (95% CI 0.45–0.85); prespecified exploratory analysis (Ann Oncol 2023)

56.5 vs 51.6 months

Median overall survival (whole population)

HR 0.92 (95% CI 0.76–1.12); P=0.4118

Drugs in this study:Bevacizumab (Avastin)Olaparib (Lynparza)

Dose and schedule cards

Olaparib + bevacizumab maintenance (PAOLA-1)

HRD-positive (BRCA mutation and/or genomic instability), advanced disease, with complete or partial response to first-line platinum-based chemotherapy plus bevacizumabEach drug’s schedule in the tableOn the page “Ovarian cancer” · First line: maintenance therapy (based on BRCA and HRD)

HRD-positive (BRCA mutation and/or genomic instability), advanced disease, with complete or partial response to first-line platinum-based chemotherapy plus bevacizumab

Drug	Dose	Route	Schedule
Olaparib	300 mg twice daily	Oral	Continuously
Bevacizumab	15 mg/kg	IV	Day 1 every 21 days

Cycle schedule: Olaparib continuously; bevacizumab every 21 days
Duration: Olaparib up to 2 years (stopping rules as in SOLO-1); bevacizumab for a total of 15 months, including the period given with chemotherapy

Olaparib monitoring and dose modification as in the previous row. Pan-Asian ESMO guideline: for BRCA-mutated and HRD-positive disease [I, A].

On the page “Ovarian cancer” · First line: maintenance therapy (based on BRCA and HRD)

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Olaparib + bevacizumab (537 patients)

Olaparib tablets 300 mg twice daily for up to 24 months, with bevacizumab 15 mg/kg every 3 weeks for a total of 15 months (including the chemotherapy period).

2Placebo + bevacizumab (269 patients)

Placebo with bevacizumab 15 mg/kg every 3 weeks for a total of 15 months.

Source of the regimen details: NEJM 2019 abstract and abstract of the final analysis in Ann Oncol 2023 (olaparib 300 mg twice daily for up to 24 months; bevacizumab 15 mg/kg every 3 weeks, 15 months in total)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients with newly diagnosed advanced high-grade ovarian cancer who had a response after first-line platinum–taxane chemotherapy plus bevacizumab; regardless of surgical outcome or BRCA mutation status.

Endpoints

Primary endpoint: time from randomisation to investigator-assessed disease progression or death (progression-free survival). Key secondary: overall survival (final analysis, Ann Oncol 2023).

Safety and side effects

Adverse events were consistent with the known safety profiles of olaparib and bevacizumab. In the final analysis, the incidence of myelodysplastic syndrome, acute myeloid leukaemia, aplastic anaemia and new primary malignancy was low and balanced between the two groups. Details of grade 3 adverse events in the full text of the paper.

Clinical significance and place in guidelines

In May 2020 the FDA approved olaparib with bevacizumab for first-line maintenance in HRD-positive tumours (BRCA mutation and/or genomic instability). The final overall survival analysis (Ray-Coquard et al., Ann Oncol 2023) showed a clinically meaningful overall survival improvement in HRD-positive disease and confirmed this combination as one of the standards of care. The ESMO guideline (Pan-Asian adapted version 2025) recommends olaparib–bevacizumab for BRCA-mutated or HRD-positive tumours [I, A].

Limitations

There was no single-agent olaparib comparator arm, so the contribution of bevacizumab in BRCA-mutated patients is unclear; HRD subgroup analyses were exploratory; the overall survival benefit in the whole population was not significant.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.