# PAOLA-1: olaparib added to bevacizumab maintenance in newly diagnosed ovarian cancer, with benefit confined to HRD-positive tumours

Source: https://onco.cc/key-papers/paper-paola-1-nejm-2019/  
OnCo record `paper-paola-1-nejm-2019` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Adding the PARP inhibitor olaparib to bevacizumab after first-line chemotherapy for advanced ovarian cancer roughly doubled the time without progression in women whose tumours had defective DNA repair, but did nothing for those without it.

## Summary

Double-blind, placebo-controlled phase 3 trial of 806 patients with newly diagnosed advanced high-grade ovarian cancer who had responded to platinum-taxane chemotherapy with bevacizumab, randomised 2:1 to two years of olaparib or placebo added to bevacizumab maintenance. Primary endpoint was investigator-assessed PFS.

Median PFS was 22.1 vs 16.6 months overall (HR 0.59), but 37.2 vs 17.7 months (HR 0.33) in homologous-recombination-deficient (HRD) tumours and no different in HRD-negative tumours (HR 1.00). The 2023 OS analysis showed a survival benefit in HRD-positive disease (5-year OS 65.5% vs 48.4%, HR 0.62). It established HRD testing as a decision tool and olaparib plus bevacizumab as a first-line maintenance standard for HRD-positive ovarian cancer.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: New England Journal of Medicine
- Year: 2019
- DOI: 10.1056/NEJMoa1911361
- Authors: Ray-Coquard I, Pautier P, Pignata S, et al.
- Findings: Overall population: median PFS 22.1 vs 16.6 months; HR 0.59 (95% CI 0.49-0.72).; HRD-positive (including BRCA-mutated): median PFS 37.2 vs 17.7 months; HR 0.33.; HRD-positive without BRCA mutation: median PFS 28.1 vs 16.6 months; HR 0.43.; HRD-negative or unknown: no benefit (HR about 1.0).; Overall survival (Annals of Oncology 2023): HRD-positive 5-year OS 65.5% vs 48.4%, HR 0.62; no OS benefit in the ITT population (HR 0.92).
- What it means: Women with newly diagnosed advanced ovarian cancer should have their tumour tested for BRCA mutations and homologous recombination deficiency, because those who are HRD-positive gain years of additional disease control and better survival from adding olaparib to bevacizumab maintenance. Those who are HRD-negative gain nothing from olaparib in this combination and should not be exposed to its toxicity and cost. HRD testing has become a routine part of ovarian cancer care as a result.
- Caveats: HRD assays (Myriad myChoice and alternatives) have imperfect concordance and a substantial proportion of tests are inconclusive.; All patients received bevacizumab, so the trial cannot say whether olaparib alone would be as good in HRD-positive non-BRCA tumours (PRIMA suggests niraparib alone works).; No ITT overall survival benefit; the HRD-positive OS result is from a prespecified subgroup.; Two years of olaparib plus bevacizumab is expensive and adds anaemia, fatigue and nausea.

## Sources

- NEJM 2019: https://doi.org/10.1056/NEJMoa1911361
- ClinicalTrials.gov NCT02477644: https://clinicaltrials.gov/study/NCT02477644

## Connected records

- cancers: [High-grade serous ovarian cancer](https://onco.cc/cancers/high-grade-serous-ovarian-cancer/), [Ovarian cancer](https://onco.cc/cancers/ovarian/), [Platinum-sensitive ovarian cancer](https://onco.cc/cancers/platinum-sensitive-ovarian-cancer/)
- technologies: [Anti-angiogenic therapy](https://onco.cc/technologies/antiangiogenic/), [HRD & BRCA testing](https://onco.cc/technologies/hrd-testing/), [PARP inhibitors](https://onco.cc/technologies/parp-inhibitor/), [Synthetic lethality approaches](https://onco.cc/technologies/synthetic-lethality-approaches/)
- targets: [BRCA1 / BRCA2 (HRD)](https://onco.cc/targets/brca/), [PARP](https://onco.cc/targets/parp/), [VEGF / VEGFR](https://onco.cc/targets/vegf/)
- drugs: [Olaparib](https://onco.cc/drugs/olaparib/)
- companies: [AstraZeneca](https://onco.cc/companies/astrazeneca/), [Merck & Co. (MSD)](https://onco.cc/companies/merck/)
- institutions: [Policlinico Universitario A. Gemelli](https://onco.cc/institutions/gemelli/)
- terms: [Germline vs somatic mutations](https://onco.cc/terms/germline-vs-somatic/), [Homologous recombination deficiency (HRD)](https://onco.cc/terms/hrd/), [Overall survival (OS)](https://onco.cc/terms/os/), [Progression-free survival (PFS)](https://onco.cc/terms/pfs/), [Synthetic lethality](https://onco.cc/terms/synthetic-lethality/)
- people: [Giovanni Scambia](https://onco.cc/people/giovanni-scambia/), [Isabelle Ray-Coquard](https://onco.cc/people/isabelle-ray-coquard/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/), [Dormant cells and minimal residual disease](https://onco.cc/bottlenecks/b-dormancy-mrd/), [Prices and value](https://onco.cc/bottlenecks/b-drug-pricing/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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