Neratinib, an Irreversible ErbB Receptor Tyrosine Kinase Inhibitor, in Patients With Advanced ErbB2-Positive Breast Cancer

Burstein, Harold J.; Sun, Yan; Dirix, Luc; Jiang, Zefei; Paridaens, Robert; Tan, Antoinette R.; Awada, Ahmad; Ranade, Anantbhushan; Jiao, Shunchang; Schwartz, Gary K.; Abbas, Richat; Powell, C. Thomas; Turnbull, Kathleen; Vermette, Jennifer; Zacharchuk, Charles; Badwe, Rajendra

doi:10.1200/jco.2009.25.8707

Cited by 454 publications

(294 citation statements)

References 22 publications

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“…An open-label, phase II multicenter trial of single-agent neratinib in 136 patients with HER2-positive MBC showed a RR of 24% in patients previously treated with trastuzumab, and a RR of 56% in trastuzumab-naïve patients. PFS at 16 weeks was 59 and 78%, respectively (72). No grade 3 or 4 cardiotoxicity related to neratinib was reported, but grade 3 and 4 diarrhea was the most frequently occurring adverse effect.…”

Section: Tyrosine Kinase Inhibitorsmentioning

confidence: 89%

Targeted therapy in HER2-positive breast cancer

2013

Biomedical Reports

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Abstract. Treatment options for breast cancer vary based on tumor surface markers and clinical factors, including cytotoxic chemotherapy, hormonal therapy, biological therapy or a combination thereof. An important molecular determinant of therapy is the human epidermal growth factor receptor 2 (HER2) positivity of the tumor, which has been identified in 20-25% of breast cancers and is a prognostic marker of poor outcome. The advent of HER2-targeted therapies has significantly improved the survival of patients with HER2-positive breast cancer. This review focuses on current HER2-targeted therapeutic options for patients with HER2-positive breast cancer, including monoclonal antibodies and tyrosine kinase inhibitors (TKIs).

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Section: Tyrosine Kinase Inhibitorsmentioning

confidence: 89%

Targeted therapy in HER2-positive breast cancer

2013

Biomedical Reports

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“…Many types of molecular targeting drugs against EGFR have been developed for various cancer types including breast cancer (41)(42)(43)(44)(45). However, despite their clinical benefits, ubiquitous expression and physiological requirement of EGFR in noncancerous tissues led to various adverse effects such as severe skin toxicities, resulting in decreased quality of life of patients and interruption or discontinuation of anti-EGFR treatment (46,47).…”

Section: Discussionmentioning

confidence: 99%

Critical involvement of RQCD1 in the EGFR-Akt pathway in mammary carcinogenesis

Ajiro

Nishidate²,

Katagiri³

et al. 2010

Int J Oncol

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Abstract. We previously reported an important role of RQCD1 in mammary carcinogenesis through the interaction with Grb10 interacting GYF protein 1 (GIGYF1), Grb10 interacting GYF protein 2 (GIGYF2) and growth factor receptor binding protein 10 (Grb10). In this study, we investigated the biological mechanism of RQCD1 in regulation of the Akt activity as the downstream signal of epidermal growth factor receptor (EGFR). Knockdown of RQCD1 reduced the Akt phosphorylation level that was induced by epidermal growth factor (EGF) stimulation. We found a possible formation of the big complex involved in the Akt activity including Akt, EGFR, GIGYF1 and GIGYF2, Grb10 and RQCD1. We subsequently defined that a region corresponding to 620-665th amino acids of GIGYF1 and 667-712th amino acids of GIGYF2 interacted with RQCD1. Furthermore, we found that RQCD1 was required for enhancement of the interaction of Grb10 with GIGYF1 and GIGYF2. Our findings in this study imply the functional mechanism of RQCD1 in the Akt activity regulation as a mediator in the EGFR-signaling pathway.

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“…[50,51]. In a phase II study, neratinib showed a median PFS of 22.3 and 39.6 weeks in 136 HER2-positive MBC patients with or without prior trastuzumab, respectively [52]. In another phase II MBC study with neratinib/vinorelbine, RRs were 41% (no prior lapatinib) and 8% (prior lapatinib) [53].…”

Section: Lapatinibmentioning

confidence: 99%

Human Epidermal Growth Factor Receptor Family-Targeted Therapies in the Treatment of HER2-Overexpressing Breast Cancer

2014

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Purpose. Chemotherapy has been tested extensively in conjunction with standard therapy in the treatment of head and neck cancer, primarily in the form of neoadjuvant chemotherapy, but few trials have shown a survival benefit. Although a few studies have suggested that adjuvant chemotherapy given after standard treatment may improve survival, to date these trials have been troubled by various problems in design and dosing. The purpose of our trial was to determine the feasibility of giving moderately intensive chemotherapy exclusively after standard therapy, and to determine whether survival appeared to be improved as measured against historical data. Methods. We used adjuvant chemotherapy in two groups of patients with squamous cell carcinoma of the head and neck: group A consisted of 46 patients with newly diagnosed stage III and IV disease, and group B consisted of 46 patients with relapsed disease having been treated with salvage surgery. In all patients, the intended adjuvant chemotherapy consisted of two cycles of combination cisplatin, bleomycin, and infusional 5‐fluorouracil (5‐FU) given three weeks apart, followed by four cycles of bolus methotrexate, 5‐FU, and bleomycin given every two weeks. Results. In group A, the two‐year survival was 72%. In group B, the two‐year survival was 58%. Conclusion. Compared to the vast majority of similarly staged patients with head and neck cancer reported in the literature, the survival of our group seemed considerably better, suggesting that a definitive randomized study testing this schedule of adjuvant chemotherapy is warranted.

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Neratinib, an Irreversible ErbB Receptor Tyrosine Kinase Inhibitor, in Patients With Advanced ErbB2-Positive Breast Cancer

Cited by 454 publications

References 22 publications

Targeted therapy in HER2-positive breast cancer

Targeted therapy in HER2-positive breast cancer

Critical involvement of RQCD1 in the EGFR-Akt pathway in mammary carcinogenesis

Human Epidermal Growth Factor Receptor Family-Targeted Therapies in the Treatment of HER2-Overexpressing Breast Cancer

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