Author
Listed:
- Jean E. Abraham
(University of Cambridge
University of Cambridge)
- Lenka Oplustil O’Connor
(AstraZeneca)
- Louise Grybowicz
(Cambridge University Hospitals NHS Foundation Trust)
- Karen Pinilla Alba
(University of Cambridge
University of Cambridge)
- Alimu Dayimu
(University of Cambridge)
- Nikolaos Demiris
(Athens University of Economics and Business)
- Caron Harvey
(Cambridge University Hospitals NHS Foundation Trust)
- Lynsey M. Drewett
(Royal Devon University Healthcare NHS Foundation Trust)
- Rebecca Lucey
(University of Cambridge
University of Cambridge)
- Alexander Fulton
(University of Cambridge
University of Cambridge)
- Anne N. Roberts
(Cambridge University Hospitals NHS Foundation Trust)
- Joanna R. Worley
(University of Cambridge
University of Cambridge)
- Ms Anita Chhabra
(Cambridge University Hospitals NHS Foundation Trust)
- Wendi Qian
(Cambridge University Hospitals NHS Foundation Trust)
- Jessica Brown
(AstraZeneca)
- Richard Hardy
(University of Cambridge)
- Anne-Laure Vallier
(Cambridge University Hospitals NHS Foundation Trust)
- Steve Chan
(Nottingham University Hospitals NHS Trust
University of Nottingham)
- Maria Esther Una Cidon
(University Hospitals Dorset NHS Foundation Trust)
- Elizabeth Sherwin
(East Suffolk and North Essex NHS Foundation Trust)
- Amitabha Chakrabarti
(University Hospitals Dorset NHS Foundation Trust)
- Claire Sadler
(Alderley Edge)
- Jen Barnes
(AstraZeneca)
- Mojca Persic
(University Hospital of Derby and Burton)
- Sarah Smith
(Bedfordshire Hospitals NHS Foundation Trust)
- Sanjay Raj
(University Hospital Southampton NHS Foundation Trust
Hampshire Hospitals NHS Foundation Trust)
- Annabel Borley
(Velindre Cancer Centre)
- Jeremy P. Braybrooke
(University Hospitals Bristol and Weston NHS Foundation Trust)
- Emma Staples
(Havering and Redbridge University Hospitals NHS Trust)
- Lucy C. Scott
(Beatson West Of Scotland Cancer Centre)
- Cheryl A. Palmer
(North West Anglia NHS Foundation Trust)
- Margaret Moody
(West Suffolk Hospital NHS Foundation Trust)
- Mark J. Churn
(Worcestershire Acute Hospitals NHS Trust)
- Domenic Pilger
(AstraZeneca)
- Guido Zagnoli-Vieira
(AstraZeneca)
- Paul W. G. Wijnhoven
(AstraZeneca)
- Mukesh B. Mukesh
(East Suffolk & North Essex NHS Trust)
- Rebecca R. Roylance
(University College London Hospitals NHS Foundation Trust)
- Philip C. Schouten
(Cambridge University Hospitals NHS Foundation Trust)
- Nicola C. Levitt
(Oxford University Hospital NHS Foundation Trust)
- Karen McAdam
(North West Anglia NHS Foundation Trust)
- Anne C. Armstrong
(The Christie NHS Foundation Trust)
- Ellen R. Copson
(University of Southampton)
- Emma McMurtry
(EMC2 Clinical Consultancy Ltd)
- Susan Galbraith
(AstraZeneca)
- Marc Tischkowitz
(University of Cambridge)
- Elena Provenzano
(Cambridge University Hospitals NHS Foundation Trust)
- Mark J. O’Connor
(AstraZeneca)
- Helena M. Earl
(University of Cambridge)
Abstract
Poly (ADP-ribose) polymerase inhibitors (PARPi) exploit DNA repair deficiency in germline BRCA1 and BRCA2 pathogenic variant (gBRCAm) cancers. Haematological toxicity limits chemotherapy-PARPi treatment combinations. In preclinical models we identified a schedule combining olaparib and carboplatin that avoids enhanced toxicity but maintains anti-tumour activity. We investigated this schedule in a neoadjuvant, phase II-III, randomised controlled trial for gBRCAm breast cancers (ClinicalTrials.gov ID:NCT03150576; PARTNER). The research arm included carboplatin (Area Under the Curve 5, 3-weekly); paclitaxel (80 mg/m2, weekly) day 1, plus olaparib (150 mg twice daily) day 3-14 (4 cycles), followed by anthracycline-containing chemotherapy (3 cycles); control arm gave chemotherapy alone. The primary endpoint, pathological complete response rate, showed no statistical difference between research 64.1% (25/39); control 69.8% (30/43) (p = 0.59). However, estimated survival outcomes at 36-months demonstrated improved event-free survival: research 96.4%, control 80.1% (p = 0.04); overall survival: research 100%, control 88.2% (p = 0.04) and breast cancer specific survival: research 100%, control 88.2% (p = 0.04). There were no statistical differences in relapse-free survival and distant disease-free survival, both were: research 96.4%, control 87.9% (p = 0.20). Similarly, local recurrence-free survival and time to second cancer were both: research 96.4%, control 87.8% (p = 0.20). The PARTNER trial identified a safe, tolerable schedule combining neoadjuvant chemotherapy with olaparib. This combination demonstrated schedule-dependent overall survival benefit in early-stage gBRCAm breast cancer. This result needs confirmation in larger trials.
Suggested Citation
Jean E. Abraham & Lenka Oplustil O’Connor & Louise Grybowicz & Karen Pinilla Alba & Alimu Dayimu & Nikolaos Demiris & Caron Harvey & Lynsey M. Drewett & Rebecca Lucey & Alexander Fulton & Anne N. Robe, 2025.
"Neoadjuvant PARP inhibitor scheduling in BRCA1 and BRCA2 related breast cancer: PARTNER, a randomized phase II/III trial,"
Nature Communications, Nature, vol. 16(1), pages 1-15, December.
Handle:
RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59151-0
DOI: 10.1038/s41467-025-59151-0
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