Platinum and Polyadenosine 5'Diphosphoribose Polymerisation Inhibitor for Neoadjuvant Treatment of Triple Negative Breast Cancer and/or Germline BRCA Positive Breast Cancer

Summary

This neoadjuvant trial for patients with TNBC and/or gBRCA breast cancer, aims to investigate the safety and efficacy (improvement in pathological Complete Response at surgery) of concurrent platinum-based chemotherapy with olaparib an inhibitor of the PARP enzyme (PARPi).

Timeline

Start

2016-05

Primary completion

2024-06

Completion

2034-06

Outcome

Missed primary endpoint

paper 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). PMID 40360463 ↗

paper pCR was achieved in 51% of patients in the research arm and 52% in the control arm (P = 0.753). PMID 38588696 ↗

paper Neoadjuvant olaparib did not improve pCR rates, EFS or OS when added to carboplatin-paclitaxel and anthracycline-based chemotherapy PMID 38588696 ↗

Publications

• Abraham JE, O'Connor LO, Grybowicz L, Alba KP, Dayimu A, Demiris N, Harvey C, Drewett LM, Lucey R, Fulton A, Roberts AN, Worley JR, Chhabra MA, Qian W, Brown J, Hardy R, Vallier AL, Chan S, Cidon MEU, Sherwin E, Chakrabarti A, Sadler C, Barnes J, Persic M, Smith S, Raj S, Borley A, Braybrooke JP, Staples E, Scott LC, Palmer CA, Moody M, Churn MJ, Pilger D, Zagnoli-Vieira G, Wijnhoven PWG, Mukesh MB, Roylance RR, Schouten PC, Levitt NC, McAdam K, Armstrong AC, Copson ER, McMurtry E, Galbraith S, Tischkowitz M, Provenzano E, O'Connor MJ, Earl HM; PARTNER Trial Group. Neoadjuvant PARP inhibitor scheduling in BRCA1 and BRCA2 related breast cancer: PARTNER, a randomized phase II/III trial. Nat Commun. 2025 May 13;16(1):4269. doi: 10.1038/s41467-025-59151-0.
• Abraham JE, Pinilla K, Dayimu A, Grybowicz L, Demiris N, Harvey C, Drewett LM, Lucey R, Fulton A, Roberts AN, Worley JR, Chhabra A, Qian W, Vallier AL, Hardy RM, Chan S, Hickish T, Tripathi D, Venkitaraman R, Persic M, Aslam S, Glassman D, Raj S, Borley A, Braybrooke JP, Sutherland S, Staples E, Scott LC, Davies M, Palmer CA, Moody M, Churn MJ, Newby JC, Mukesh MB, Chakrabarti A, Roylance RR, Schouten PC, Levitt NC, McAdam K, Armstrong AC, Copson ER, McMurtry E, Tischkowitz M, Provenzano E, Earl HM. The PARTNER trial of neoadjuvant olaparib with chemotherapy in triple-negative breast cancer. Nature. 2024 May;629(8014):1142-1148. doi: 10.1038/s41586-024-07384-2. Epub 2024 Apr 8.
• Woitek R, McLean MA, Ursprung S, Rueda OM, Manzano Garcia R, Locke MJ, Beer L, Baxter G, Rundo L, Provenzano E, Kaggie J, Patterson A, Frary A, Field-Rayner J, Papalouka V, Kane J, Benjamin AJV, Gill AB, Priest AN, Lewis DY, Russell R, Grimmer A, White B, Latimer-Bowman B, Patterson I, Schiller A, Carmo B, Slough R, Lanz T, Wason J, Schulte RF, Chin SF, Graves MJ, Gilbert FJ, Abraham JE, Caldas C, Brindle KM, Sala E, Gallagher FA. Hyperpolarized Carbon-13 MRI for Early Response Assessment of Neoadjuvant Chemotherapy in Breast Cancer Patients. Cancer Res. 2021 Dec 1;81(23):6004-6017. doi: 10.1158/0008-5472.CAN-21-1499. Epub 2021 Oct 8.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Olaparib	Small molecule	150 mg	Oral
Background	Carboplatin	Small molecule	5 unknown	Intravenous
Background	Paclitaxel	Small molecule	80 mg/m2	Intravenous

Indications