Long-Term Cardiac Tolerability of Trastuzumab in Metastatic Breast Cancer: The M.D. Anderson Cancer Center Experience

Guarneri, Valentina; Lenihan, Daniel J.; Valero, Vicente; Durand, Jean Bernard; Broglio, Kristine; Hess, Kenneth R.; Michaud, Laura Boehnke; González-Angulo, Ana M.; Hortobágyi, Gabriel N.; Esteva, Francisco J.

doi:10.1200/jco.2005.04.9551

Cited by 339 publications

(223 citation statements)

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“…Trastuzumab treatment is associated with cardiac dysfunction, with up to 28% of patients experiencing such events (Guarneri et al, 2006), although asymptomatic LVEF declines were more common than symptomatic heart failure (Marty et al, 2003). In this study, three patients experienced LVEF decrease (2.4%); however, with mild severity (Grade 1).…”

Section: Discussionmentioning

confidence: 99%

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Lapatinib monotherapy in patients with relapsed, advanced, or metastatic breast cancer: efficacy, safety, and biomarker results from Japanese patients phase II studies

et al. 2009

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BACKGROUND: HER2-positive metastatic breast cancer (MBC) relapsing after trastuzumab-based therapy may require continued HER2 receptor inhibition to control the disease and preserve the patients' quality-of-life. Efficacy and safety of lapatinib monotherapy was evaluated in Japanese breast cancer patients after trastuzumab-based therapies. METHODS: In studies, EGF100642 and EGF104911 evaluated the efficacy and safety of oral lapatinib given 1500 mg once daily in patients with advanced or MBC. All patients progressed on anthracyclines and taxanes; HER2-positive patients had also progressed on trastuzumab. RESULTS: For HER2-positive tumours (n ¼ 100), objective response rate was 19.0% (95% confidence interval (CI): 11.8 -28.1) and clinical benefit rate (CBR) was 25.0% (95% CI: 16.9 -34.7). One out of 22 HER2-negative tumour was documented as complete response (n ¼ 22). The median time-to-progression (TTP) in the HER2-positive and HER2-negative groups was 13.0 and 8.0 weeks (P ¼ 0.007); median overall survival was 58.3 and 40.0 weeks, respectively. The most frequent adverse event was diarrhoea. TTP and CBR were significantly associated with HER2 expression. Patients with tumours harbouring an H1047R PIK3CA mutation or low expression of PTEN derived clinical benefit from lapatinib. CONCLUSION: Lapatinib monotherapy had shown anti-tumour activity in Japanese patients with HER2-positive MBC that relapsed after trastuzumab-based therapy, including those with brain metastases. Patients benefiting from lapatinib may have biomarker profiles differing from that reported for trastuzumab.

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Section: Discussionmentioning

confidence: 99%

“…Intrinsic and acquired trastuzumab resistance remains a concern (Nahta and Esteva, 2006;Xia et al, 2007). Additional concerns include increased incidence of brain metastasis and risk of both short-and long-term cardiac toxicity associated with trastuzumab therapy (Guarneri et al, 2006;Suter et al, 2007).…”

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confidence: 99%

Lapatinib monotherapy in patients with relapsed, advanced, or metastatic breast cancer: efficacy, safety, and biomarker results from Japanese patients phase II studies

et al. 2009

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“…In a retrospective analysis of older women with early‐stage breast cancer, compared with patients who did not receive either adjuvant chemotherapy or trastuzumab, use of trastuzumab alone or the combination of trastuzumab and anthracycline were associated with absolute increases in the adjusted incidence rate of HF or cardiomyopathy of 14% and 23.8% 51. Similarly, in a retrospective analysis of women treated for metastatic breast cancer at the MD Anderson where 5% had a history of cardiovascular disease (CVD), 26.5% of those who received HER2 targeted therapies had symptomatic HF, which was reversible in the majority of cases 52. Data from the health maintenance organization Cancer Research Network reported the cumulative incidence of HF at 1 and 5 years was 6.2% and 20.1% for women who received a combination of anthracycline and trastuzumab and 3.6% and 12.1% for women who received trastuzumab alone 50.…”

Section: Risk Of Cardiotoxicity Outside Of Clinical Trialsmentioning

confidence: 99%

Cardiotoxicity From Human Epidermal Growth Factor Receptor‐2 (HER2) Targeted Therapies

Florido

Smith

Cuomo

et al. 2017

JAHA

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“…Unlike the anthracyclines, there is no evidence that cumulative doses can predict for cardiomyopathy with trastuzumab. Guidelines advise that patients suffering heart failure due to anticancer agents are managed similarly to those with heart failure due to other causes [13]. However, it is unclear whether cancer patients respond similarly to non-cancer patients.…”

Section: Hepatotoxicitymentioning

confidence: 99%

The changing paradigm for supportive care in cancer patients

Chan

Lees

Keefe

2014

Support Care Cancer

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Dear Editor, With scientific advances in cancer supportive care and the incorporation of effective supportive care strategies into contemporary cancer treatment, there has been a substantial reduction in the occurrence of severe toxicities traditionally associated with cytotoxic chemotherapy over the past two decades. For example, appropriate prophylaxis with antiemetics (including a 5-HT 3 antagonist, corticosteroid, and NK-1 antagonist) has greatly reduced chemotherapy-induced nausea and vomiting, colony-stimulating factors have curbed febrile neutropenia, and the integrated use of mouth care and palifermin has decreased the severity of oral mucositis. In addition, the introduction of structured management and care pathways into clinical practice has widely promoted these supportive care strategies for patients. We may not currently have all the answers on the prevention of chemotherapyinduced toxicities, but most oncology clinicians today can capably handle toxicities which were previously considered difficult to manage.Innovations in cancer therapeutics have improved the oncologist's toolkit to cure and control many cancers previously difficult to manage. Targeted therapy agents are now commonly used in the management of cancers ranging from chronic myeloid leukemia to renal cell carcinoma, and new indications and increased lines of therapy continue to arise. Initially "targeted" drugs were thought to have unique mechanisms for targeting cancer cells and were considered to produce fewer side effects than traditional cytotoxic chemotherapy. Importantly, however, clinicians are now observing a number of emerging and highly prevalent side effects associated with the use of targeted therapies [1]. These agents, which carry with them significant financial cost, are also associated with an increase in chronic complications that can decrease a patient's quality of life [2]. We must, therefore, strive to understand and be responsive to the side effects of these novel therapeutics to enable optimal patient adherence to and participation in their treatment.In this commentary, we highlight toxicities that are commonly associated with targeted therapies, namely dermatological, gastrointestinal (diarrhea and stomatitis), hepatotoxicity, cardiotoxicity, neurotoxicity, and immunotoxicity. More importantly, we will emphasize the current impediments to understanding the mechanisms behind emerging side effects and the lack of effective strategies for managing these toxicities. Dermatological toxicitiesCommonly associated with targeted agents is a range of dermatological toxicities, which are different from the skin toxicities seen with traditional cytotoxic chemotherapy. The first of these class-related skin toxicities is observed with epidermal growth factor receptor inhibitors (EGFRI), including agents used for the treatment of lung (gefitinib, erlotinib, and afatinib), pancreatic (erlotinib), breast (lapatinib), head and neck (cetuximab), and colorectal cancers (cetuximab and panitumumab). They usually manifest as papulopu...

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Long-Term Cardiac Tolerability of Trastuzumab in Metastatic Breast Cancer: The M.D. Anderson Cancer Center Experience

Cited by 339 publications

References 32 publications

Lapatinib monotherapy in patients with relapsed, advanced, or metastatic breast cancer: efficacy, safety, and biomarker results from Japanese patients phase II studies

Lapatinib monotherapy in patients with relapsed, advanced, or metastatic breast cancer: efficacy, safety, and biomarker results from Japanese patients phase II studies

Cardiotoxicity From Human Epidermal Growth Factor Receptor‐2 (HER2) Targeted Therapies

The changing paradigm for supportive care in cancer patients

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