Addition of BIBW 2992, an irreversible inhibitor of EGFR/HER1 and HER2, to letrozole in estrogen receptor (ER)-positive metastatic breast cancer (mBC) progressing on letrozole monotherapy.

Gunzer, K.; Mont-Serrat, H. de; Uttenreuther-Fischer, Martina; Misset, J.-L.; team, trial

doi:10.1200/jco.2010.28.15_suppl.1072

Cited by 8 publications

(9 citation statements)

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“…Results of an open-label phase II study in advanced HER2-positive breast cancer patients after failure of trastuzumab were recently published, showing clinical benefit in 53% of the patients enrolled 79. Additional phase II studies showed acceptable tolerance and moderate activity of afatinib in ER-positive, HER2-negative breast cancer patients 82-84.…”

Section: Small Molecule Her/egfr Inhibitors Other Than Lapatinibmentioning

confidence: 99%

Treating Breast Cancer in the 21st Century: Emerging Biological Therapies

et al. 2013

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For many years, the medical treatment of breast cancer was reliant solely on cytotoxic chemotherapy. However, over the past twenty years, treatment has evolved to a more target-directed approach. We now employ tailored therapy based on the presence or absence of receptors for estrogen, progesterone, and human epidermal growth factor 2 (HER2). We expect this trend to continue, as agents that use novel approaches to target HER2, as well as targeting different portions of the HER signaling pathway, are in various stages of development. Notably, pertuzumab, a humanized monoclonal antibody that binds to a different domain of the extracellular portion of the HER2 receptor than trastuzumab, was recently approved for use, as was lapatinib, a small-molecule tyrosine kinase inhibitor. Patients with triple negative breast cancer, particularly those with the BRCA mutation, have more limited treatment options and carry a worse prognosis than those who are hormone receptor positive. However, recent data has shown that PARP inhibitors may have significant anti-tumor effect in those with this subtype of breast cancer. Novel agents that inhibit mTOR, PI3K, the insulin-like growth factor, heat shock protein 90, and histone deacetylase have shown promise in phase I-III trials and offer exciting new possibilities for the treatment of this often fatal disease. As we are presented with an ever increasing number of treatment options, the timing and combinations of therapeutic agents used becomes ever more complex in the age of personalized care, but we are hopeful that ultimately this will lead to improved patient outcomes.

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Section: Small Molecule Her/egfr Inhibitors Other Than Lapatinibmentioning

confidence: 99%

Treating Breast Cancer in the 21st Century: Emerging Biological Therapies

et al. 2013

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“…At the 2010 ASCO annual meeting, Gunzer and colleagues presented results from an open-label singlearm Phase II study with afatinib added to letrozole following disease progression on letrozole monotherapy. 26 Primary endpoint was the rate of nonprogression at 16 weeks of therapy. A total of 28 mainly HER2-negative patients from 30 enrolled patients have been treated.…”

Section: Activity In Breast Cancermentioning

confidence: 99%

Potential of afatinib in the treatment of patients with HER2-positive breast cancer

Geuna

Montemurro

Aglietta³

et al. 2012

BCTT

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Abstract:In the absence of treatment, overexpression of the human epidermal growth factor receptor 2 (HER2) predicts a poor prognosis in breast cancer. In the last decade, monoclonal antibodies and small molecule tyrosine kinase inhibitors have significantly improved the outcome of HER2-positive breast cancer patients. However, tumor resistance and toxicities often limit the use of these therapies. For this reason, there is a compelling need for further investigation of new targeted therapies, such as afatinib, an oral irreversible pan inhibitor of the epidermal growth factor receptor (EGFR) family. This compound covalently interacts with tyrosine kinase domains, which are deeply involved in signal transduction leading to cell proliferation and protection from apoptosis. Afatinib has been studied in several Phase I clinical trials in advanced solid tumors. These trials have shown encouraging clinical activity and manageable side effects when afatinib is used either as a single agent or in combination with chemotherapy, with cutaneous adverse events and diarrhea being the most frequently observed toxicities. This review will focus on afatinib's clinical activity and will discuss ongoing clinical studies in HER2-positive breast cancer patients. In the scenario of the different HER2-targeted therapies, it will be important to define the best specific clinical and "molecular" setting for afatinib use, trying to identify predictors of resistance and response. Moreover, afatinib, which has the ability to cross the blood-brain barrier, could play a role in patients with brain metastases from breast cancer.

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“…Three phase II trials had been previously conducted in patients with metastatic breast cancer (19)(20)(21). Four of 35 patients showed a partial response (PR) and 15 stable metastatic breast cancers with afatinib monotherapy after failure of prior trastuzumab treatment.…”

Section: Introductionmentioning

confidence: 99%

“…Mean duration of response was 153 days (19). Five of 28 patients included into a combination trial with afatinib and letrozole in estrogen receptor (ER)-positive, hormone-refractory, mostly HER2-negative patients had stabilization of disease for more than four cycles (20). A phase I study revealed a maximum tolerated dose of 20 mg afatinib when given in combination with weekly trastuzumab with diarrhea being the leading toxicity in 31% of patients (22).…”

Section: Introductionmentioning

confidence: 99%

Dual Blockade with AFatinib and Trastuzumab as NEoadjuvant Treatment for Patients with Locally Advanced or Operable Breast Cancer Receiving Taxane–Anthracycline Containing Chemotherapy—DAFNE (GBG-70)

Hanusch

Schneeweiß

Loibl

et al. 2015

Clinical Cancer Research

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Purpose: Dual anti-HER2 blockade with trastuzumab/pertuzumab or trastuzumab/lapatinib in combination with anthracycline/taxane-based chemotherapy can reach pathologic complete response (pCR) rates of up to 60% in HER2-positive breast cancer. The DAFNE (Dual blockade with AFatinib and trastuzumab as NEoadjuvant treatment) phase II study (NCT015591477) investigated a dual blockade with the irreversible pan-HER inhibitor afatinib and trastuzumab in this setting.Experimental Design: Participants with untreated, centrally HER2-positive breast cancer were treated for 6 weeks with afatinib (20 mg/d) and trastuzumab [(8) 6 mg/kg/3 weeks] alone; followed by 12-week treatment with paclitaxel (80 mg/m 2 /1 week), trastuzumab, and afatinib; followed by 12 weeks with epirubicin (90 mg/m 2 /3 weeks), cyclophosphamide (600 mg/m 2 /3 weeks), and trastuzumab before surgery. Primary objective was pCR rate, defined as ypT0/is ypN0. We expected a pCR rate of 70%; 65 patients were needed to exclude a rate of 55%.Results: pCR rate was 49.2% [90% confidence interval (CI), 38.5-60.1] in 65 treated patients. Patients with hormone receptor-negative (N ¼ 19) or hormone receptor-positive (N ¼ 46) tumors showed pCR rates of 63.2% and 43.5%, respectively (P ¼ 0.153). Patients with (N ¼ 9) or without (N ¼ 56) lymphocyte predominant breast cancer (LPBC) showed pCR rates of 100% and 41.1%, respectively (P < 0.001). PCR rate was not different in patients with or without PIK3CA tumor mutations (P ¼ 0.363). Clinical responses were seen in 96.3% of 54 evaluable patients, and breast conserving surgery was possible in 59.4% of 62 assessable patients. Most frequent nonhematologic grade 3-4 toxicities were diarrhea (7.7%), increased creatinine (4.6%), and infection (4.6%). One patient developed symptomatic congestive heart failure.Conclusions: Neoadjuvant treatment with afatinib, trastuzumab, and chemotherapy showed acceptable tolerability, and a pCR rate comparable with that of other anti-HER2 doublets but below challenging expectations.

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Addition of BIBW 2992, an irreversible inhibitor of EGFR/HER1 and HER2, to letrozole in estrogen receptor (ER)-positive metastatic breast cancer (mBC) progressing on letrozole monotherapy.

Cited by 8 publications

References 0 publications

Treating Breast Cancer in the 21st Century: Emerging Biological Therapies

Treating Breast Cancer in the 21st Century: Emerging Biological Therapies

Potential of afatinib in the treatment of patients with HER2-positive breast cancer

Dual Blockade with AFatinib and Trastuzumab as NEoadjuvant Treatment for Patients with Locally Advanced or Operable Breast Cancer Receiving Taxane–Anthracycline Containing Chemotherapy—DAFNE (GBG-70)

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