scholarly journals Case Report: Significant Efficacy of Pyrotinib in the Treatment of Extensive Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer Cutaneous Metastases: A Report of Five Cases

2021 ◽  
Vol 11 ◽  
Author(s):  
Nan Wang ◽  
Lin Li ◽  
Youyi Xiong ◽  
Jiangrui Chi ◽  
Xinwei Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Cutaneous Metastasis ◽  
Her2 Positive ◽  
Cutaneous Metastases ◽  
Human Epidermal Growth Factor ◽  
Epidermal Growth

BackgroundBreast cancer (BC) is the most common tumor to develop cutaneous metastases. Most BCs with cutaneous metastasis are human epidermal growth factor receptor 2 (HER2)-positive subtypes. Although the molecular mechanisms of breast cancer metastasis to different sites and the corresponding treatment methods are areas of in-depth research, there are few studies on cutaneous metastasis.Case PresentationFive HER2-positive BC patients with extensive cutaneous metastases were treated with a regimen containing pyrotinib, a novel small-molecule tyrosine kinase inhibitor that irreversibly blocks epidermal growth factor receptor (EGFR), HER2, and human epidermal growth factor receptor 4 (HER4), then their cutaneous metastases quickly resolved at an astonishing speed and their condition was well controlled during the follow-up period.ConclusionsThis case series reports the significant therapeutic effect of pyrotinib on cutaneous metastases of HER2-positive BC for the first time. Based on this, we recommend that pyrotinib can be used as a supplement to trastuzumab for HER2-positive BC patients with cutaneous metastases. In addition, we should consider that the pan-inhibitory effect of pyrotinib on EGFR, HER2, and HER4 may provide a dual therapeutic effect against HER2 and mucin 1.

scholarly journals Optimum duration of adjuvant trastuzumab in treatment of human epidermal growth factor receptor-2 positive early breast cancer: protocol for a network meta-analysis of randomised controlled trials

BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e035802
Author(s):  
Qiancheng Hu ◽  
Xin Wang ◽  
Ye Chen ◽  
Xiaofen Li ◽  
Ting Luo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Early Breast Cancer ◽  
Meta Analysis ◽  
Growth Factor Receptor ◽  
Her2 Positive ◽  
Human Epidermal Growth Factor ◽  
Epidermal Growth

IntroductionControversy regarding optimum duration of trastuzumab treatment remains in patients with human epidermal growth factor receptor-2 (HER2) positive early breast cancer. The objective of applying network meta-analysis (NMA) is to integrate existing evidence based on direct and indirect comparisons of efficacy and safety, and then to determine the duration of trastuzumab treatments with the greatest impact on therapeutic outcomes in HER2-positive early breast cancers.Methods and analysisElectronic searching of trastuzumab treatments for early breast cancer by titles and abstracts will be conducted for the period from inception to 16 June 2019 in PubMed, Cochrane Library, Embase and ClinicalTrils.gov, as well as the annual meetings of San Antonio Breast Cancer Symposium (SABCS), European Society of Medical Oncology (ESMO) and American Society of Clinical Oncology (ASCO) online archives. The outcomes of interest are overall survival, disease-free survival, acceptability, cardiotoxicities and grade 3 to 4 non-haematological toxicities. Two independent reviewers will screen and extract eligible data based on the inclusion and exclusion criteria, and then assess the risk of bias and evidence quality of individual studies using Cochrane Collaboration’s tool and Grades of Recommendation, Assessment, Development and Evaluation (GRADE). The heterogeneity, transitivity and inconsistency of NMA will be evaluated. In addition, we will perform subgroup and sensitivity analyses to assess the robustness and reliability of findings in our NMA.Ethics and disseminationEthics approval is not required for our NMA. Findings from our NMA will be submitted as peer-reviewed journal manuscripts and international conference reports.Trial registration numberCRD42019139109.

Exploring mechanisms of acquired resistance to HER2 (human epidermal growth factor receptor 2)-targeted therapies in breast cancer

2014 ◽  
Vol 42 (4) ◽  
pp. 822-830 ◽  
Author(s):  
Helen Creedon ◽  
Adam Byron ◽  
Joanna Main ◽  
Larry Hayward ◽  
Teresa Klinowska ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Acquired Resistance ◽  
Growth Factor Receptor ◽  
Resistance Mechanisms ◽  
Her2 Positive ◽  
Human Epidermal Growth Factor ◽  
Epidermal Growth

HER2 (human epidermal growth factor receptor 2)-targeted therapy in breast cancer is one of the earliest and arguably most successful examples of the modern class of targeted drugs. Initially identified in the 1980s, the observation that HER2 acts as an independent predictor of poor prognosis in the 20% of breast cancer cases carrying a gene amplification or protein overexpression cemented its place at the forefront of research in this field. The outlook for patients with HER2-positive breast cancer has been revolutionized by the introduction of HER2-targeted agents, such as trastuzumab and lapatinib, yet resistance is frequently encountered and multiple different resistance mechanisms have been identified. We have explored resistance to a novel pan-HER inhibitor, AZD8931, and we examine mechanisms of resistance common to trastuzumab, lapatinib and AZD8931, and discuss the current problems associated with translating the wealth of pre-clinical data into clinical benefit.

Randomized Trial of Lapatinib Versus Placebo Added to Paclitaxel in the Treatment of Human Epidermal Growth Factor Receptor 2–Overexpressing Metastatic Breast Cancer

2013 ◽  
Vol 31 (16) ◽  
pp. 1947-1953 ◽  
Author(s):  
Zhongzhen Guan ◽  
Binghe Xu ◽  
Michelle L. DeSilvio ◽  
Zhenzhou Shen ◽  
Wichit Arpornwirat ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Metastatic Breast Cancer ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Her2 Positive ◽  
Human Epidermal Growth Factor ◽  
Epidermal Growth

Purpose Lapatinib is an oral small-molecule tyrosine kinase inhibitor of both epidermal growth factor receptor and human epidermal growth factor receptor 2 (HER2). This study is designed to test whether the addition of lapatinib to paclitaxel improves overall survival (OS) compared with placebo plus paclitaxel in patients with HER2-overexpressing metastatic breast cancer (MBC). Patients and Methods This phase III, randomized, double-blind study assessed the efficacy and safety of lapatinib plus paclitaxel compared with placebo plus paclitaxel in patients with newly diagnosed HER2-positive MBC. The primary end point was OS. Secondary end points included progression-free survival (PFS), overall response rate (ORR), clinical benefit rate, and safety. Results The addition of lapatinib to paclitaxel significantly improved OS versus paclitaxel (treatment hazard ratio [HR], 0.74; 95% CI, 0.58 to 0.94; P = .0124); median OS was 27.8 versus 20.5 months, respectively. Median PFS was prolonged by 3.2 months, from 6.5 months with placebo plus paclitaxel to 9.7 months with lapatinib plus paclitaxel (HR, 0.52; 95% CI, 0.42 to 0.64; stratified log-rank P < .001). ORR was significantly higher with lapatinib plus paclitaxel compared with placebo plus paclitaxel (69% v 50%, respectively; P < .001). The incidence of grades 3 and 4 diarrhea and neutropenia was higher in the lapatinib plus paclitaxel arm. Only 4% of patients in this group reported febrile neutropenia. Cardiac events were low grade, asymptomatic, and mostly reversible. The incidence of hepatic events was similar in both arms. There were no fatal adverse events in the lapatinib plus paclitaxel arm. Conclusion This trial demonstrated that lapatinib combined with paclitaxel offers a significant and clinically meaningful survival advantage over paclitaxel alone in patients with HER2-positive MBC.

Lapatinib or Trastuzumab Plus Taxane Therapy for Human Epidermal Growth Factor Receptor 2–Positive Advanced Breast Cancer: Final Results of NCIC CTG MA.31

2015 ◽  
Vol 33 (14) ◽  
pp. 1574-1583 ◽  
Author(s):  
Karen A. Gelmon ◽  
Frances M. Boyle ◽  
Bella Kaufman ◽  
David G. Huntsman ◽  
Alexey Manikhas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
First Line ◽  
Her2 Positive ◽  
Human Epidermal Growth Factor ◽  
End Point ◽  
Epidermal Growth

Purpose The efficacy of lapatinib versus trastuzumab combined with taxanes in the first-line setting of human epidermal growth factor receptor 2 (HER2) –positive metastatic breast cancer (BC) is unknown. Patients and Methods The MA.31 trial compared a combination of first-line anti-HER2 therapy (lapatinib or trastuzumab) and taxane therapy for 24 weeks, followed by the same anti-HER2 monotherapy until progression. Stratification was by prior (neo)adjuvant anti-HER2 therapy, prior (neo)adjuvant taxane, planned taxane, and liver metastases. The primary end point was intention-to-treat (ITT) progression-free survival (PFS), defined as time from random assignment to progression by RECIST (version 1.0) criteria, or death for patients with locally assessed HER2-positive tumors. The primary test statistic was a stratified log-rank test for noninferiority. PFS was also assessed for patients with centrally confirmed HER2-positive tumors. Results From July 17, 2008, to December 1, 2011, 652 patients were accrued from 21 countries, resulting in 537 patients with centrally confirmed HER2-positive tumors. Median follow-up was 21.5 months. Median ITT PFS was 9.0 months with lapatinib and 11.3 months with trastuzumab. By ITT analysis, PFS was inferior for lapatinib compared with trastuzumab, with a stratified hazard ratio (HR) of 1.37 (95% CI, 1.13 to 1.65; P = .001). In patients with centrally confirmed HER2-positive tumors, median PFS was 9.1 months with lapatinib and 13.6 months with trastuzumab (HR, 1.48; 95% CI, 1.20 to 1.83; P < .001). More grade 3 or 4 diarrhea and rash were observed with lapatinib (P < .001). PFS results were supported by the secondary end point of overall survival, with an ITT HR of 1.28 (95% CI, 0.95 to 1.72; P = .11); in patients with centrally confirmed HER2-positive tumors, the HR was 1.47 (95% CI, 1.03 to 2.09; P = .03). Conclusion As first-line therapy for HER2-positive metastatic BC, lapatinib combined with taxane was associated with shorter PFS and more toxicity compared with trastuzumab combined with taxane.

scholarly journals Multicenter Phase II Study of Neoadjuvant Lapatinib and Trastuzumab With Hormonal Therapy and Without Chemotherapy in Patients With Human Epidermal Growth Factor Receptor 2–Overexpressing Breast Cancer: TBCRC 006

2013 ◽  
Vol 31 (14) ◽  
pp. 1726-1731 ◽  
Author(s):  
Mothaffar F. Rimawi ◽  
Ingrid A. Mayer ◽  
Andres Forero ◽  
Rita Nanda ◽  
Matthew P. Goetz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Targeted Therapy ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Her2 Positive ◽  
Human Epidermal Growth Factor ◽  
Er Positive ◽  
Epidermal Growth

Purpose We previously reported the eradication of human epidermal growth factor receptor 2 (HER2)– amplified human xenografts in mice by inhibition of the HER2 pathway with lapatinib and trastuzumab to block all homo- and heterodimer signaling as well as by blockade of estrogen receptor (ER) when expressed. In this clinical trial, we sought to translate these findings to patients using targeted therapy without chemotherapy. Patients and Methods Women with stages II to III HER2-positive breast cancers were eligible. They received trastuzumab once per week (4 mg/kg loading, then 2 mg/kg) and lapatinib 1000 mg once per day for 12 weeks. Women with ER-positive tumors also received letrozole (plus a luteinizing hormone–releasing hormone [LHRH] agonist if premenopausal). Pathologic response was assessed by ER status. Biopsies were obtained at baseline, weeks 2 and 8, and time of surgery. Results Sixty-six patients were enrolled, and 64 were eligible and evaluable for response. Median tumor size was 6 cm (range, 1.5 to 30 cm). Adverse events were mainly grades 1 to 2 (GI, 63%; skin, 46%). Grade 3 metabolic, GI, and liver (18%; 12 patients) and grade 4 liver toxicities (one patient) were also observed. Overall, in-breast pathologic complete response (pCR; ypT0-is) was 27% (ER positive, 21%; ER negative, 36%). The rate of low-volume residual disease (ypT1a-b) was 22% (ER positive, 33%; ER negative, 4%). Conclusion In patients with locally advanced HER2-positive breast cancer, our approach of targeted therapy only resulted in a high pCR rate without chemotherapy. Our data support the hypothesis that selected patients with HER2-positive tumors may not need chemotherapy, and more-complete blockade of HER receptors and ER is an effective strategy worthy of further study.

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