Olaparib versus chemotherapy treatment of physician’s choice in patients with a germline <i>BRCA</i> mutation and HER2-negative metastatic breast cancer (OlympiAD): Efficacy in patients with visceral metastases.

Tung, Nadine; Im, Seock‐Ah; Senkus-Konefka, E.; Xu, Binghe; Domchek, Susan M.; Masuda, Norikazu; Li, Wei; Armstrong, Anne; Conte, Pier Franco; Wu, Weiwen; Goessl, Carsten; Runswick, Sarah

doi:10.1200/jco.2018.36.15_suppl.1052

Cited by 11 publications

(8 citation statements)

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“…ORR in the olaparib arm was more than double the rate observed with TPC when assessed by blinded independent central review (59.9% vs. 28.8%) [29], and also when investigator-assessed (57.6% vs. 22.2%) [32]. Similarly, ORR with olaparib was more than double that with TPC in patients with visceral metastases (lung/pleura, liver, and brain/central nervous system) in post hoc analyses [74].…”

Section: Olaparib In the Phase 3 Olympiad Trialmentioning

confidence: 82%

“…PFS HRs were consistent across a range of patient subgroups, including those with and those without prior exposure to chemotherapy for metastatic BC and in patients with TNBC, an important consideration given the limited treatment options available for TNBC [29]. Post hoc analyses suggested that patients with visceral metastases benefit from improvements in PFS, when investigated by location (lung/pleura, liver, and brain/central nervous system) [74]. Another post hoc analysis showed that, in the few patients whose tumors did not show loss of heterozygosity (6% of 125 tested patients), there was no evidence for a reduction in the efficacy of olaparib, based on PFS [30].…”

Section: Olaparib In the Phase 3 Olympiad Trialmentioning

confidence: 89%

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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: Olaparib In the Phase 3 Olympiad Trialmentioning

confidence: 82%

Section: Olaparib In the Phase 3 Olympiad Trialmentioning

confidence: 89%

An Overview of PARP Inhibitors for the Treatment of Breast Cancer

2021

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“…Outside of ovarian cancer, olaparib and talazoparib were approved by the FDA to treat gBRCAm, HER2-negative, locally advanced, or metastatic breast cancer patients who have received treatment with an anthracycline and/or a taxane (unless contraindicated) in the neoadjuvant, adjuvant, and/or metastatic treatment setting. Both approvals were based on significant improvement of PFS when compared to physician’s choice of chemotherapy in the randomized OlympiAD (NCT02000622) and EMBRACA (NCT01945775) trials [18,19].…”

Section: Current Food and Drug Administration-approved Parp Inhibimentioning

confidence: 99%

Clinical Development of PARP Inhibitors in Treating Metastatic Castration-Resistant Prostate Cancer

Adashek

Jain

Zhang

2019

Cells

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The approval of upfront abiraterone for castration-sensitive prostate cancer and the approval of enzalutamide and apalutamide for non-metastatic castration-resistant prostate cancer have led to early utilization of potent androgen receptor (AR) signaling inhibitors in treating advanced prostate cancer. There is an unmet need to develop novel therapies beyond targeting AR signaling for metastatic castration-resistant prostate cancer (mCRPC). Poly (ADP-ribose) polymerase inhibitors (PARPi) belong to a class of targeted agents being developed for the treatment of homologous recombination repair (HRR) deficient tumors. Olaparib, rucaparib, niraparib, veliparib, and talazoparib were evaluated in early phase trials as a monotherapy for HRR-deficient mCRPC. Among them, olaparib and rucaparib have breakthrough designations for BRCA1/2-mutated mCRPC. Phase II studies also reported clinical activity of the PARPi and abiraterone combination and the PARPi checkpoint inhibitor combination in HRR-intact mCRPC. Ongoing phase III trials are testing these combinations as frontline or later line treatments for mCRPC. This review summarizes the critical clinical data as well as ongoing clinical trials for developing PARPi in treating mCRPC.

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“…The PFS benefit was consistent, regardless of prior platinum therapy or baseline BRCA1/2 mutations but was more evident among TNBC versus HR+/HER2− mBC patients (10). Furthermore, in comparison with the standard therapy, olaparib showed PFS benefits in patients with liver metastases and central nervous system (CNS) metastases (11).…”

Section: Study Resultsmentioning

confidence: 86%

Optimizing the management of HER2-negative metastatic breast cancer in the era of PARP inhibitors—proceedings from breast cancer expert group meeting

et al. 2020

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The therapeutic landscape of human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (mBC) has evolved considerably with the introduction of newer targeted agents such as poly-ADP ribose polymerase inhibitors (PARPi), novel chemotherapeutic agents, immunotherapy, and endocrine therapies. In this scenario, optimizing the appropriate treatment sequence is a daunting task for clinicians. To develop evidence-based answers to key clinical questions on treatment selection and appropriate treatment sequence for the management of patients with HER2− mBC in the era of PARPi, a breast cancer expert group meeting was convened. The expert panel comprised of eight key opinion leaders from Argentina,

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Olaparib versus chemotherapy treatment of physician’s choice in patients with a germline BRCA mutation and HER2-negative metastatic breast cancer (OlympiAD): Efficacy in patients with visceral metastases.

Cited by 11 publications

References 0 publications

An Overview of PARP Inhibitors for the Treatment of Breast Cancer

An Overview of PARP Inhibitors for the Treatment of Breast Cancer

Clinical Development of PARP Inhibitors in Treating Metastatic Castration-Resistant Prostate Cancer

Optimizing the management of HER2-negative metastatic breast cancer in the era of PARP inhibitors—proceedings from breast cancer expert group meeting

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