PARTNER: Randomised, phase II/III trial to evaluate the safety and efficacy of the addition of olaparib to platinum-based neoadjuvant chemotherapy in triple negative and/or germline BRCA mutated breast cancer patients.

Abraham, Jean; Vallier, Anne-Laure; Qian, Wendi; Machin, Andrea; Grybowicz, Louise; Thomas, S J; Harvey, Caron; McAdam, Karen; Hughes-Davies, Luke; Roylance, Rebecca; Copson, Ellen; Provenzano, Elena; Pinilla, Karen; McMurtry, Emma; Tischkowitz, Marc; Earl, Helena

doi:10.1200/jco.2018.36.15_suppl.tps605

Cited by 5 publications

(3 citation statements)

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“…TNBCs often harbor somatic BRCA or other HRR mutations, or BRCA genes may be silenced through promoter hypermethylation, which may result in susceptibility to PARP inhibitor therapy [ 137 ]. PARTNER is a three-stage phase 2/3 trial, designed to assess the safety, schedule selection, and efficacy of neoadjuvant olaparib in combination with platinum-based chemotherapy for patients with TNBC and/or gBRCA-mutated BC [ 138 , 139 ]. Based on 159 patients (target N = 527), preliminary safety data support the combination.…”

Section: Overview Of New Directions For Parp Inhibitorsmentioning

confidence: 99%

An Overview of PARP Inhibitors for the Treatment of Breast Cancer

2021

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Loss-of-function mutations in BRCA1 and BRCA2 are detected in at least 5% of unselected patients with breast cancer (BC). These BC susceptibility genes encode proteins critical for DNA homologous recombination repair (HRR). This review provides an update on oral poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of BC. Olaparib and talazoparib are PARP inhibitors approved as monotherapies for deleterious/suspected deleterious germline BRCA-mutated, HER2-negative BC. Olaparib is approved in the USA for metastatic BC and in Europe for locally advanced/metastatic BC. Talazoparib is approved for locally advanced/metastatic BC in the USA and Europe. In phase 3 trials, olaparib and talazoparib monotherapies demonstrated significant progression-free survival benefits compared with chemotherapy. Common toxicities were effectively managed by supportive treatment and dose interruptions/reductions. Veliparib combined with platinum-based chemotherapy has also shown promise for locally advanced/metastatic BC in a phase 3 trial. Differences in efficacy and safety across PARP inhibitors (olaparib, talazoparib, veliparib, niraparib, rucaparib) may relate to differences in potency of PARP trapping on DNA and cytotoxic specificity. PARP inhibitors are being investigated in early BC, in novel combinations, and in patients without germline BRCA mutations, including those with somatic BRCA mutations and other HRR gene mutations. Ongoing phase 2/3 studies include PARP inhibitors combined with immune checkpoint inhibitors for the treatment of triple-negative BC. Wider access to testing for BRCA and other mutations, and to genetic counseling, are required to identify patients who could benefit from PARP inhibitor therapy. The advent of PARP inhibitors has potential benefits for BC treatment beyond the locally advanced/metastatic setting.

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Section: Overview Of New Directions For Parp Inhibitorsmentioning

confidence: 99%

An Overview of PARP Inhibitors for the Treatment of Breast Cancer

2021

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“…As yet, there is no definitive evidence to either support or refute the use of PARPi in the non-g BRCA TNBC population. An ongoing neoadjuvant study (NCT03150576) that includes both sporadic TNBC and BRCA -associated tumours will help elucidate the value of gBRCA mutations in predicting the response to the addition of PARPi to platinum-based chemotherapy ( 100 ). Furthermore, no biomarker was predicted for benefit from Pembrolizumab in the KEYNOTE-522 trial, despite the encouraging response rates shown.…”

Section: Discussionmentioning

confidence: 99%

“…Single-agent cisplatin has shown conflicting results for BRCA carriers ( 96 ). The PARTNER (NCT03150576) trial includes a cohort of gBRCA -mutated patients ( 100 ) and will help elucidate the effect of platinum and PARPi in this subgroup.…”

Section: Targetable Molecular Pathwaysmentioning

confidence: 99%

Precision Breast Cancer Medicine: Early Stage Triple Negative Breast Cancer—A Review of Molecular Characterisation, Therapeutic Targets and Future Trends

et al. 2022

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Personalised approaches to the management of all solid tumours are increasing rapidly, along with wider accessibility for clinicians. Advances in tumour characterisation and targeted therapies have placed triple-negative breast cancers (TNBC) at the forefront of this approach. TNBC is a highly heterogeneous disease with various histopathological features and is driven by distinct molecular alterations. The ability to tailor individualised and effective treatments for each patient is of particular importance in this group due to the high risk of distant recurrence and death. The mainstay of treatment across all subtypes of TNBC has historically been cytotoxic chemotherapy, which is often associated with off-target tissue toxicity and drug resistance. Neoadjuvant chemotherapy is commonly used as it allows close monitoring of early treatment response and provides valuable prognostic information. Patients who achieve a complete pathological response after neoadjuvant chemotherapy are known to have significantly improved long-term outcomes. Conversely, poor responders face a higher risk of relapse and death. The identification of those subgroups that are more likely to benefit from breakthroughs in the personalised approach is a challenge of the current era where several targeted therapies are available. This review presents an overview of contemporary practice, and promising future trends in the management of early TNBC. Platinum chemotherapy, DNA damage response (DDR) inhibitors, immune checkpoint inhibitors, inhibitors of the PI3K-AKT-mTOR, and androgen receptor (AR) pathways are some of the increasingly studied therapies which will be reviewed. We will also discuss the growing evidence for less-developed agents and predictive biomarkers that are likely to contribute to the forthcoming advances in this field. Finally, we will propose a framework for the personalised management of TNBC based upon the integration of clinico-pathological and molecular features to ensure that long-term outcomes are optimised.

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