140O Veliparib plus carboplatin-paclitaxel in patients with HER2-negative advanced/metastatic gBRCA-associated breast cancer: Results in hormone receptor-positive and triple-negative breast cancer subgroups from the phase III BROCADE3 trial

Ayoub, J-P.; Friedlander, Michael; Dièras, Véronique; Wildiers, Hans; Arun, Banu K.; Han, Hyo S.; Puhalla, Shannon; Shparyk, Yaroslav; Jakobsen, Erik; Kundu, Madan G.; Wu, Meijing; Ratajczak, Christine K.; Maag, David; Kaufman, Bella

doi:10.1016/j.annonc.2020.03.241

Cited by 5 publications

(4 citation statements)

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“…The median OS was 35.0 and 30.0 months, respectively. 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.…”

Section: The Role Of Platinum-based Chemotherapymentioning

confidence: 77%

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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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Section: The Role Of Platinum-based Chemotherapymentioning

confidence: 77%

Section: Poly(adp-ribose) Polymerase Inhibitors In Mtnbcmentioning

confidence: 77%

Emerging Therapeutic Drugs in Metastatic Triple-Negative Breast Cancer

Cipriano

Mesquita

2021

Breast Cancer�(Auckl)

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“…Median PFS in the TNBC group was 16.6 months in the veliparib-plus-carboplatin-paclitaxel arm vs. 14.1 months in the placebo-plus-carboplatin-paclitaxel arm (HR 0.72). In the same subgroup, the trial also showed an OS improvement in the experimental arm (35 vs. 30, HR 0.69) [ 43 ].…”

Section: Targeting Intracellular Pathwaysmentioning

confidence: 99%

Personalised Therapies for Metastatic Triple-Negative Breast Cancer: When Target Is Not Everything

Capici¹,

Carlofrancesco

Nicole

et al. 2022

Cancers

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Triple-negative breast cancer—defined by the absence of oestrogen/progesterone receptors and human epidermal growth factor receptor 2 expression—is a complex and heterogeneous type of tumour characterised by poor prognosis, aggressive behaviour and lack of effective therapeutic strategies. The identification of new biomarkers and molecular signatures is leading to development of new therapeutic strategies including immunotherapy, targeted therapy and antibody-drug conjugates (ADCs). Against a background where chemotherapy has always been considered the standard of care, evolution towards a precision medicine approach could improve TNBC clinical practice in a complex scenario, with many therapeutic options and new drugs. The aim of this review was to focus on emerging therapeutic targets and their related specific therapy, discussing available and emerging drugs, underlining differences in approval by American and European regulatory authorities and showing the future perspective in the large number of ongoing clinical trials.

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“…PARPib are also being evaluated in combination with chemotherapeutic agents (91)(92)(93)(94). In the phase 3 BROCADE3 trial (N = 509), addition of veliparib to carboplatin and paclitaxel resulted in a significant improvement in median PFS compared with placebo plus carboplatin and paclitaxel (14.5 vs. 12.6 months; HR: 0.71, 95% CI: 0.57-0.88; p = 0.002) in patients with gBRCA-mutated, HER2-negative, locally advanced or metastatic BC (105,106). The PFS benefit was durable, and no additional toxicities were seen, although there was a high degree of toxicity in both treatment arms (105).…”

Section: Parp Inhibitors and Chemotherapymentioning

confidence: 99%

Emerging Role of PARP Inhibitors in Metastatic Triple Negative Breast Cancer. Current Scenario and Future Perspectives

et al. 2021

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Triple negative tumors represent 15% of breast cancer and are characterized by the lack of estrogen receptors, progesterone receptor, and HER2 amplification or overexpression. Approximately 25% of patients diagnosed with triple negative breast cancer carry a germline BRCA1 or BRCA2 mutation. They have an aggressive biology, and chemotherapy has been the mainstay of treatment for a long time. Despite intensive therapies, prognosis is still poor, and many patients will eventually relapse or die due to cancer. Therefore, novel targeted agents that can increase the treatment options for this disease are urgently needed. Recently, a new class of molecules has emerged as a standard of care for patients with triple negative breast cancer and germline BRCA1 or BRCA2 mutation: poly (ADP-ribose) (PARP) inhibitors. In the first part of the review, we summarize and discuss evidence supporting the use of PARP inhibitors. Currently, two PARP inhibitors have been approved for triple negative metastatic breast cancer—olaparib and talazoparib—based on two phase III trials, which showed a progression-free survival benefit when compared to chemotherapy. Safety profile was manageable with supportive therapies and dose reductions/interruptions. In addition, other PARP inhibitors are currently under investigation, such as talazoparib, rucaparib, and veliparib. Subsequently, we will discuss the potential role of PARP inhibitors in the future. Clinical research areas are investigating PARP inhibitors in combination with other agents and are including patients without germline BRCA mutations: ongoing phase II/III studies are combining PARP inhibitors with immunotherapy, while phases I and II trials are combining PARP inhibitors with other targeted agents such as ATM and PIK3CA inhibitors. Moreover, several clinical trials are enrolling patients with somatic BRCA mutation or patients carrying mutations in genes, other than BRCA1/2, involved in the homologous recombination repair pathway (e.g., CHECK2, PALB2, RAD51, etc.).

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140O Veliparib plus carboplatin-paclitaxel in patients with HER2-negative advanced/metastatic gBRCA-associated breast cancer: Results in hormone receptor-positive and triple-negative breast cancer subgroups from the phase III BROCADE3 trial

Cited by 5 publications

References 0 publications

Emerging Therapeutic Drugs in Metastatic Triple-Negative Breast Cancer

Emerging Therapeutic Drugs in Metastatic Triple-Negative Breast Cancer

Personalised Therapies for Metastatic Triple-Negative Breast Cancer: When Target Is Not Everything

Emerging Role of PARP Inhibitors in Metastatic Triple Negative Breast Cancer. Current Scenario and Future Perspectives

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