Weekly Paclitaxel and Carboplatin Plus Bevacizumab as First-Line Treatment of Metastatic Triple-Negative Breast Cancer. A Multicenter Phase II Trial by the Hellenic Oncology Research Group

Saloustros, Emmanouil; Nikolaou, Michail; Kalbakis, K.; Polyzos, Aris; Christofillakis, Charalampos; Kentepozidis, Nikolaos; Pistamaltzian, Nikolaos; Kourousis, Charalampos; Vamvakas, L.; Georgoulias, V.; Mavroudis, Dimitris

doi:10.1016/j.clbc.2017.10.013

Cited by 18 publications

(12 citation statements)

References 26 publications

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“…The chemotherapeutic strategies for treating TNBC primarily include DNA-damaging agents, antimitotic agents, and targeted antiangiogenic therapy. For example, the combination use of carboplatin, paclitaxel, and bevacizumab, respectively, is recommended as a firstline or second-line therapy for TNBC treatment (51)(52)(53). However, novel chemotherapies are required to improve the survival rates for TNBC due to taxane-induced dose-limiting neurotoxicities or cardiotoxicities and acquired resistance to taxanes (54).…”

Section: Discussionmentioning

confidence: 99%

An Orally Available Tubulin Inhibitor, VERU-111, Suppresses Triple-Negative Breast Cancer Tumor Growth and Metastasis and Bypasses Taxane Resistance

Deng

Krutilina

Wang

et al. 2020

Molecular Cancer Therapeutics

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Triple-negative breast cancer (TNBC) accounts for approximately 15% of breast cancer cases in the United States. TNBC has poorer overall prognosis relative to other molecular subtypes due to rapid onset of drug resistance to conventional chemotherapies and increased risk of visceral metastases. Taxanes like paclitaxel are standard chemotherapies that stabilize microtubules, but their clinical efficacy is often limited by drug resistance and neurotoxicities. We evaluated the preclinical efficacy of a novel, potent, and orally bioavailable tubulin inhibitor, VERU-111, in TNBC models. VERU-111 showed potent cytotoxicity against TNBC cell lines, inducing apoptosis and cell-cycle arrest in a concentrationdependent manner. VERU-111 also efficiently inhibited colony formation, cell migration, and invasion. Orally administered VERU-111 inhibited MDA-MB-231 xenograft growth in a dose-dependent manner, with similar efficacies to paclitaxel, but without acute toxicity. VERU-111 significantly reduced metastases originating from the mammary fat pad into lung, liver, and kidney metastasis in an experimental metastasis model. Moreover, VERU-111, but not paclitaxel, suppressed growth of luciferase-labeled, taxane-resistant, patient-derived metastatic TNBC tumors. In this model, VERU-111 repressed growth of preestablished axillary lymph node metastases and lung, bone, and liver metastases at study endpoint, whereas paclitaxel enhanced liver metastases relative to vehicle controls. Collectively, these studies strongly suggest that VERU-111 is not only a potent inhibitor of aggressive TNBC phenotypes, but it is also efficacious in a taxane-resistant model of metastatic TNBC. Thus, VERU-111 is a promising new generation of tubulin inhibitor for the treatment of TNBC and may be effective in patients who progress on taxanes.Results presented in this study demonstrate the efficacy of VERU-111 in vivo and provide strong rationale for future development of VERU-111 as an effective treatment for metastatic breast cancer.

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Section: Discussionmentioning

confidence: 99%

An Orally Available Tubulin Inhibitor, VERU-111, Suppresses Triple-Negative Breast Cancer Tumor Growth and Metastasis and Bypasses Taxane Resistance

Deng

Krutilina

Wang

et al. 2020

Molecular Cancer Therapeutics

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“…Further, a meta-analysis [204] found that the combination treatment of bevacizumab plus taxane-based chemotherapy is associated with an additional 2.7 month increased PFS in advanced TNBC patients. Notably, a multicenter phase II clinical trial concluded that weekly treatment of paclitaxel and carboplatin with bevacizumab as neoadjuvant in advanced TNBC patients result in clinically favorable PFS [206]. Similarly, another phase II clinical study [207] investigated the effect of bevacizumab and erlotinib (an EGF receptor inhibitor) maintenance therapy preceded by treatment of nab-paclitaxel and bevacizumab on mTNBC (metastatic TNBC) patients, which resulted in 9.1 months of increased PFS.…”

Section: Angiogenesis Inhibitorsmentioning

confidence: 99%

Triple Negative Breast Cancer: A Mountain Yet to Be Scaled Despite the Triumphs

Siddharth

Sharma

2021

Cancers

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Metastatic progression and tumor recurrence pertaining to TNBC are certainly the leading cause of breast cancer-related mortality; however, the mechanisms underlying TNBC chemoresistance, metastasis, and tumor relapse remain somewhat ambiguous. TNBCs show 77% of the overall 4-year survival rate compared to other breast cancer subtypes (82.7 to 92.5%). TNBC is the most aggressive subtype of breast cancer, with chemotherapy being the major approved treatment strategy. Activation of ABC transporters and DNA damage response genes alongside an enrichment of cancer stem cells and metabolic reprogramming upon chemotherapy contribute to the selection of chemoresistant cells, majorly responsible for the failure of anti-chemotherapeutic regime. These selected chemoresistant cells further lead to distant metastasis and tumor relapse. The present review discusses the approved standard of care and targetable molecular mechanisms in chemoresistance and provides a comprehensive update regarding the recent advances in TNBC management.

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“…The most common grade ≥3 TRAEs with bevacizumab-containing regimens were neutropenia, sensory neuropathy, and hypertension. 49 In recent years, some optimized combination regimens have also shown satisfactory outcomes in advanced TNBC -weekly paclitaxel and carboplatin plus bevacizumab: 10.3-month median PFS and 25.7-month median OS 50 and nab-paclitaxel plus bevacizumab followed by bevacizumab and erlotinib (anti-EGFR) maintenance therapy: 9.1-month median PFS, 18.1-month median OS, and 74% partial response rate. 51 In addition, long ncRNA encoded 60-amino acid polypeptide (ASRPS), centromere protein U, endogenous hydrogen sulfide, and exosomal-annexin A2 have been found to be associated with angiogenesis and suggested to be potential targets.…”

Section: Angiogenesis Inhibitorsmentioning

confidence: 99%

<p>Progress: Targeted Therapy, Immunotherapy, and New Chemotherapy Strategies in Advanced Triple-Negative Breast Cancer</p>

Shi

Liu

Song

2020

CMAR

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Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer, accounting for approximately 15% of cases, and is defined by the lack of expression of hormone receptors (estrogen and progesterone receptors) and lack of amplification or overexpression of human epidermal growth receptor 2 (HER2). Due to the lack of targets of hormone receptors and HER2, treatment of TNBC or advanced TNBC relies on conventional chemotherapeutic agents, but their efficacy and prognosis are poor. In patients with advanced TNBC, poorer outcomes are observed. Recently, with the launch of clinical trials and advancements in molecular studies, targeted therapy for signaling transduction pathways, immunotherapy for immune checkpoints, and new chemotherapy strategies have provided feasible or potential therapeutic options for advanced TNBC. This review aimed to summarize recent progress in targeted therapy, immunotherapy, and chemotherapy for advanced TNBC.

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Weekly Paclitaxel and Carboplatin Plus Bevacizumab as First-Line Treatment of Metastatic Triple-Negative Breast Cancer. A Multicenter Phase II Trial by the Hellenic Oncology Research Group

Cited by 18 publications

References 26 publications

An Orally Available Tubulin Inhibitor, VERU-111, Suppresses Triple-Negative Breast Cancer Tumor Growth and Metastasis and Bypasses Taxane Resistance

An Orally Available Tubulin Inhibitor, VERU-111, Suppresses Triple-Negative Breast Cancer Tumor Growth and Metastasis and Bypasses Taxane Resistance

Triple Negative Breast Cancer: A Mountain Yet to Be Scaled Despite the Triumphs

<p>Progress: Targeted Therapy, Immunotherapy, and New Chemotherapy Strategies in Advanced Triple-Negative Breast Cancer</p>

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