Veliparib with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer (BROCADE3): a randomised, double-blind, placebo-controlled, phase 3 trial

Dièras, Véronique; Han, Hyo S.; Kaufman, Bella; Wildiers, Hans; Friedlander, Michael; Ayoub, Jean-Pierre; Puhalla, Shannon; Бондаренко, И. Н.; Campone, Mario; Jakobsen, Erik; Jalving, Mathilde; Oprean, Cristina; Palácová, Markéta; Park, Yeon Hee; Shparyk, Yaroslav; Yáñez, Eduardo; Khandelwal, Nikhil; Kundu, Madan G.; Dudley, Matthew W.; Ratajczak, Christine K.; Maag, David; Arun, Banu K.

doi:10.1016/s1470-2045(20)30447-2

Cited by 247 publications

(219 citation statements)

References 26 publications

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“…94 In BROCADE 3 with veliparib, only 4% of patients had a history of CNS metastases; the evidence of efficacy on BCBMs is therefore limited. 95 Veliparib is the first PARP inhibitor to be tested specifically in BCBM; it was used in combination with WBRT in a Phase 1 trial recruiting patients with BM from primary solid tumours. 96 Median OS in the breast cancer group was 8 months (2.8-15.0 months) vs an OS of 4.9 months predicted by nomogram modelling.…”

Section: Parp Inhibitorsmentioning

confidence: 99%

Treatment strategies for breast cancer brain metastases

2020

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Brain metastases from breast cancer (BCBM) constitute the second most common cause of brain metastasis (BM), and the incidence of these frequently lethal lesions is currently increasing, following better systemic treatment. Patients with ER-negative and HER2positive metastatic breast cancer (BC) are the most likely to develop BM, but if this diagnosis remains associated with a worse prognosis, long survival is now common for patients with HER2-positive BC. BCBM represents a therapeutic challenge that needs a coordinated treatment strategy along international guidelines. Surgery has always to be considered when feasible. It is now well established that stereotaxic radiosurgery allows for equivalent control and less-cognitive toxicities than whole-brain radiation therapy, which should be delayed as much as possible. Medical treatment for BCBM is currently a rapidly evolving field. It has been shown that the blood-brain barrier (BBB) is often impaired in macroscopic BM, and several chemotherapy regimens, antibody-drug conjugates and tyrosine-kinase inhibitors have been shown to be active on BCBM and can be part of the global treatment strategy. This paper provides an overview of the therapeutic option for BCBM that is currently available and outlines potential new approaches for tackling these deadly secondary tumours.

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Section: Parp Inhibitorsmentioning

confidence: 99%

Treatment strategies for breast cancer brain metastases

2020

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“…48 There were no significant differences in the two subgroups relating QoL evaluation through EORTC QLQ-C30, QLQ-BR23, EQ-5D-5L, and Brief Pain Inventory. 49 This year, the results from SWOG S1416 were presented at the American Society of Clinical Oncology 2020 annual meeting. This phase II study evaluated the combination of cisplatin 75 mg/m 2 with veliparib or placebo 400 mg bid days 1 to 14 in a 21-day-cycle in pretreated with <1 prior line.…”

Section: The Role Of Platinum-based Chemotherapymentioning

confidence: 99%

Emerging Therapeutic Drugs in Metastatic Triple-Negative Breast Cancer

Cipriano

Mesquita

2021

Breast Cancer�(Auckl)

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Metastatic triple-negative breast cancer (TNBC) is a heterogeneous disease with a poor prognosis and currently with few treatment options. Treatment of these patients is highly based on systemic chemotherapy. Some targeted drugs were recently approved for these patients: two poly(ADP-ribose) polymerase inhibitors in patients with germline BRCA1/2 mutations (olaparib and talazoparib), immune checkpoint inhibitors in association with chemotherapy if programmed death-ligand 1 positive (atezolizumab plus nabpaclitaxel and pembrolizumab plus chemotherapy [nabpaclitaxel, paclitaxel, and carboplatin plus gemcitabine]), and an antibody-drug conjugate sacituzumab-govitecan in heavily pretreated patients (at least 2 previous lines for the metastatic setting). Combinations using these and other targeted treatment options are under investigation in early and late clinical trials, and we will probably have some practice-changing results in the new future. Other targeted drugs explored in phase II and phase III clinical trials are PI3K/AKT pathway inhibitors and androgen receptor antagonists in patients with alterations in these signaling pathways. The definition of molecular subtypes has been essential for the development of these treatment strategies. Soon, the treatment of metastatic TNBC could be based on personalized medicine using molecular testing for targeted drugs instead of only systemic chemotherapy. The authors present a review of emerging treatment options in metastatic TNBC, focusing on targeted drugs, including the recent data published in 2020.

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“…Consequently, PARPis have been the subject of investigation in several clinical trials assessing their benefit in BRCA ‐mutated breast cancer. Several studies in advanced breast cancer, including ICEBERG1, OlympiAD, EMBRACA and BROCADE3 have demonstrated benefit for PARP inhibition in advanced BRCA ‐mutated TNBC, 110‐113 and these studies are summarized in Table 4. On the basis of these results, the FDA approved the use of olaparib to treat patients with HER2 negative breast cancer in the presence of a germline BRCA mutation.…”

Section: Hr Defects and Cancer Treatmentmentioning

confidence: 99%

Homologous recombination deficiency in breast cancer: Implications for risk, cancer development, and therapy

Ali

McIntosh

Savage

2020

Genes Chromosomes & Cancer

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An underlying cause of breast cancers has been largely attributed to defects in the DNA damage response (DDR) pathway. In particular, the homologous recombination (HR) pathway repairs double‐stranded breaks (DSBs) in DNA, ultimately protecting the cell from genomic instability and thus preventing the accumulation of transforming mutations. In line with this, mutations in a number of genes encoding HR proteins are a well‐studied cause of HR deficiency (HRD), and, at the germline level, can confer risk to breast cancer but also occur somatically, contributing to sporadic breast cancer development, progression and response to therapy. Our understanding of the biological processes involved in HR and how these become compromised during breast cancer development has led to a better understanding of how HRD cells can be targeted with specific DNA damaging agents and/or with synthetic lethal targeting approaches such as PARP inhibition. Additionally, in vitro and preclinical modeling has supported the development of clinical trials to assess targeted therapies such as PARP inhibitors (PARPis), ultimately leading to development of therapies with greater clinical benefit. A number of challenges have been encountered, including resistance to therapy; however, addressing these challenges head‐on and continually driving scientific research and clinical trials with innovative therapies will contribute to our ability to target HRD in breast cancers. Ongoing research efforts into HRD in breast cancer development are therefore essential, even in the era of targeted therapies, to provide innovative strategies for improved tumor responses.

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Veliparib with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer (BROCADE3): a randomised, double-blind, placebo-controlled, phase 3 trial

Cited by 247 publications

References 26 publications

Treatment strategies for breast cancer brain metastases

Treatment strategies for breast cancer brain metastases

Emerging Therapeutic Drugs in Metastatic Triple-Negative Breast Cancer

Homologous recombination deficiency in breast cancer: Implications for risk, cancer development, and therapy

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