First-Line Trastuzumab Plus Epirubicin and Cyclophosphamide Therapy in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer: Cardiac Safety and Efficacy Data From the Herceptin, Cyclophosphamide, and Epirubicin (HERCULES) Trial

Untch, Michael; Muscholl, M.; Tjulandin, Sergei; Jonat, W.; Meerpohl, Hans-Gerd; Lichinitser, Mikhail; Manikhas, A.; Coumbos, A.; Kreienberg, R.; Bois, Andreas du; Harbeck, Nadia; Jackisch, Christian; Müller, Volkmar; Pauschinger, Matthias; Thomssen, Christoph; Lehle, Michaela; Catalani, Olivier; Lück, Hans-Joachim

doi:10.1200/jco.2009.21.9709

Cited by 64 publications

(25 citation statements)

References 24 publications

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“…Furthermore, additive cardiac toxicity might have been expected had the investigators selected an epirubicin-based triplet based upon previous studies of trastuzumab with doxorubicin in breast cancer [Seidman et al 2002], although more recent studies have safely combined trastuzumab with moderate cumulative doses (360 mg/m 2 ) of the less cardiotoxic epirubicin [Untch et al 2010]. With the doublet regimen selected for the ToGA trial, trastuzumab added little toxicity, with no increase in chemotherapy related grade 3-4 toxicities (68% both arms) or cardiac events (6% both arms), although a numerical increase in treatment related deaths was observed (3% compared with 1%).…”

Section: Clinical Evaluation Of Trastuzumab In Gastroesophageal Cancermentioning

confidence: 99%

Trastuzumab: a novel standard option for patients with HER-2-positive advanced gastric or gastro-oesophageal junction cancer

Okines

Cunningham

2012

Therap Adv Gastroenterol

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Abstract:The human epidermal receptor-2 (HER-2) is amplified in up to 25% of patients with gastroesophageal adenocarcinomas. Although the presence of this amplification does not appear to confer a poor prognosis, it provides a valuable novel therapeutic target for this group of patients. Trastuzumab is a fully humanized monoclonal antibody directed at HER-2 which binds the external domain of the receptor and exerts its action via a combination of antibodydependent cytotoxicity, reduced shedding of the extracellular domain, inhibition of dimerization and possibly receptor downregulation. The ToGA trial was an international multicentre randomized phase III study which evaluated the addition of trastuzumab to a cisplatin plus fluoropyrimidine chemotherapy doublet in 594 patients with HER-2-positive advanced gastric or oesophagogastric junction adenocarcinoma. The combination of the antibody with chemotherapy significantly improved response rate, median progression-free survival and median overall survival without additional toxicity or adversely affecting quality of life. Accordingly, trastuzumab plus chemotherapy is now a standard first-line treatment option for patients with advanced HER-2-positive gastroesophageal cancer. Unfortunately, many patients with HER-2-positive cancer exhibit primary resistance to trastuzumab and the remainder will acquire resistance to the antibody; therefore, urgent investigation into novel agents which may circumvent resistance mechanisms is warranted. Small molecule inhibitors of HER-2, which commonly also target other members of the HER family of receptors, such as EGFR and HER-3, are currently undergoing evaluation in gastroesophageal cancer as first-line alternatives to trastuzumab and second-line salvage treatments for trastuzumab-resistant disease. Extrapolating the successful use of trastuzumab in the advanced disease setting, clinical trials are underway to assess the role of this antibody in the perioperative and adjuvant settings, where it is hoped that it will have a meaningful impact upon the currently poor survival rates.

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Section: Clinical Evaluation Of Trastuzumab In Gastroesophageal Cancermentioning

confidence: 99%

Trastuzumab: a novel standard option for patients with HER-2-positive advanced gastric or gastro-oesophageal junction cancer

Okines

Cunningham

2012

Therap Adv Gastroenterol

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“…36,37 Of 445 patients treated with a neoadjuvant trastuzumab-based regimen in the GeparQuattro study, 32% achieved a pCR in breast and nodes. 22 The NOAH trial reported a statistically significant improvement in pCR with the addition of trastuzumab to neoadjuvant chemotherapy (38% vs 19%, for with and without trastuzumab, respectively; P = 0.001, in breast and lymph nodes). The same trial also reported a statistically significant improvement in the 3-year event-free survival rate (71% vs 56%, for with and without trastuzumab, respectively; HR: 0.59; 95% CI: 0.38-0.90; P = 0.013).…”

Section: Trastuzumabmentioning

confidence: 99%

“…15 Many Phase II and III studies have evaluated the combination of trastuzumab with chemotherapy for MBC in the first-line setting and beyond, yielding response rates ranging from 30% to 70%. [16][17][18][19][20][21][22][23][24][25] Trastuzumab has also been given in combination with hormonal manipulation. In the Phase III randomized TANDEM (Trastuzumab in Dual HER2 ERPositive Metastatic Breast Cancer) study, 207 patients with HER2+ and hormone receptor-positive MBC were randomly assigned to receive anastrozole alone or with trastuzumab.…”

Section: Trastuzumabmentioning

confidence: 99%

Role of lapatinib alone or in combination in the treatment of HER2-positive breast cancer

Hurvitz¹,

Kakkar²

2012

BCTT

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Purpose: This review aims to present the preclinical and clinical data regarding efficacy and safety of lapatinib alone and in combination with other agents in the treatment of human epidermal growth factor receptor-2 (HER2)-overexpressing breast cancer. Background: HER2-positive (HER2+) breast cancer remains a treatment challenge. It is more aggressive than other breast cancers and it is associated with a poor outcome. Targeted therapy for HER2+ breast cancer has significantly changed the clinical course of the disease. Despite advances in therapy, there remains an unmet need in the treatment of HER2+ breast cancer. Lapatinib is a novel, orally bioavailable epidermal growth factor receptor/HER2+ targeted agent. Many trials have investigated the efficacy and safety of lapatinib alone and in conjunction with other agents in the treatment of HER2+ breast cancer. Methods and results: Preclinical and clinical trials of lapatinib have shown that it is effective in the treatment on HER2+ breast cancer. More important, studies show that it is effective in the setting of trastuzumab resistance and in the treatment of central nervous system metastases, both of which are current treatment challenges. Furthermore, lapatinib is effective in conjunction with trastuzumab in the treatment of early breast cancer. Data regarding the safety of lapatinib show that it is generally well tolerated; however, multiple studies have shown significant (grade 3 and 4) diarrhea and rash associated with lapatinib, thereby limiting its use. Carditoxicity has not been a significant adverse event associated with the use of lapatinib. Conclusion: Lapatinib is effective alone and in conjunction with other agents in the treatment of HER2+ breast cancer. However, its use is limited by significant diarrhea and rash.

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“…40 Recently, an interesting randomized phase II trial in HER2-positive metastatic breast cancer demonstrated that the association of the less-cardiotoxic anthracycline epirubicin at a low dose (60 mg/sqm) with trastuzumab is able to induce a significant amount of durable responses (57%) and low cardiac toxicity (only 1.7% of dose-limiting cardiac toxicity). 112 Moreover, most of the trials associating liposomal anthracyclines with trastuzumab in metastatic disease revealed low incidence of symptomatic cardiac events. 50,[53][54][55][56][57] The CREC also reviewed a number of trastuzumab monotherapy trials and found a 3%-7% range of cardiac dysfunction.…”

Section: Cardiac Toxicity In Metastatic Breast Cancermentioning

confidence: 99%

Role of trastuzumab in the management of HER2-positive metastatic breast cancer

Milani

Montemurro

Gioeni

et al. 2010

BCTT

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Breast cancer is a major health issue in developed countries. Overexpression of HER2, a member of epidermal growth factor receptor family, occurs in 20%-30% of breast cancers. HER2 drives the cancer cells to develop a more aggressive phenotype, to metastasize to viscera and central nervous system, and to be less sensitive to chemotherapeutic agents. Trastuzumab (Herceptin  ) is a monoclonal antibody directed against the extracellular domain of HER2. As single agent or with chemotherapy, trastuzumab improves survival of HER2-positive breast cancers. In the past years, trastuzumab has completely revolutionized the scenario of the treatment of HER2-positive breast cancer, representing one of the most remarkable examples of targeted therapy in oncology. However, issues such as the best chemotherapeutic companion to associate with trastuzumab, cardiac toxicities, and clinical resistance still require tremendous efforts by researchers. Here, we review pharmacology, efficacy studies, and toxicities of trastuzumab in metastatic breast cancer. Moreover, we provide some insights on resistance to therapy. Finally, we briefly discuss trastuzumab's place in the clinical setting.

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First-Line Trastuzumab Plus Epirubicin and Cyclophosphamide Therapy in Patients With Human Epidermal Growth Factor Receptor 2–Positive Metastatic Breast Cancer: Cardiac Safety and Efficacy Data From the Herceptin, Cyclophosphamide, and Epirubicin (HERCULES) Trial

Cited by 64 publications

References 24 publications

Trastuzumab: a novel standard option for patients with HER-2-positive advanced gastric or gastro-oesophageal junction cancer

Trastuzumab: a novel standard option for patients with HER-2-positive advanced gastric or gastro-oesophageal junction cancer

Role of lapatinib alone or in combination in the treatment of HER2-positive breast cancer

Role of trastuzumab in the management of HER2-positive metastatic breast cancer

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