Open-label phase III randomized controlled trial comparing taxane-based chemotherapy (Tax) with lapatinib (L) or trastuzumab (T) as first-line therapy for women with HER2+ metastatic breast cancer: Interim analysis (IA) of NCIC CTG MA.31/GSK EGF 108919.

Gelmon, Karen A.; Boyle, Frances; Kaufman, Bella; Huntsman, David; Manikhas, Alexey; Leo, Angelo Di; Martı́n, Miguel; Schwartzberg, Lee S.; Dent, Susan; Ellard, Susan; Tonkin, Katia; Nagarwala, Yasir M.; Pritchard, Kathleen I.; Whelan, Timothy J.; Nomikos, Dora; Chapman, Judy‐Anne W.; Parulekar, Wendy R.

doi:10.1200/jco.2012.30.18_suppl.lba671

Cited by 49 publications

(27 citation statements)

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“…At the event-driven interim analysis, with a median follow-up of 13.6 months, patients on the lapatinib arm (n ϭ 318) experienced a significantly shorter median PFS (8.8 months vs. 11.4 months; HR ϭ 1.33; 95% CI ϭ 1.06 -1.67; p ϭ .01) ( Table 3) and comparable OS (HR ϭ 1.1; 95% CI ϭ 0.75-1.61; p ϭ .62) compared with the trastuzumab-containing regimens (n ϭ 318) [50]. Lapatinib was associated with higher rates of treatment discontinuation caused by toxicity (17.8% vs. 10.6%), and grade 3/4 diarrhea and rash (19.3% vs. 1.3% and 8.9% vs. 0.3%; p Ͻ .001), but fewer reductions in left ventricular ejection fraction (decrease of Ն20% at 36 weeks, 0% vs. 2%).…”

Section: Second Generation Her-2-directed Therapymentioning

confidence: 99%

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HER Story: The Next Chapter in HER-2-Directed Therapy for Advanced Breast Cancer

et al. 2013

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Untreated human epidermal growth factor receptor‐2 (HER‐2)‐positive advanced breast cancer (ABC) is an aggressive disease, associated with a poor prognosis and short overall survival. HER‐2‐directed therapy prolongs both time to disease progression and overall survival when combined with chemotherapy and has become the standard of care for those with HER‐2‐positive breast cancer in the early and advanced settings. Despite the remarkable therapeutic impact HER‐2‐directed therapy has had on disease outcomes, some patients with HER‐2‐positive disease will have primary resistant disease and others will respond initially but will eventually have progression, underscoring the need for other novel therapeutic options. This article reviews recent phase III trial data and discusses a practical approach to sequencing of HER‐2‐directed therapy in patients with HER‐2‐positive ABC. The significant cumulative survival gains seen in these trials are slowly reshaping the landscape of HER‐2‐positive ABC outcomes.

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Section: Second Generation Her-2-directed Therapymentioning

confidence: 99%

“…Despite initial concerns, relatively low rates of cardiotoxicity (grade 3 left ventricular systolic dysfunction: 0%-2.8%) have been reported for standard or emerging HER-2-directed therapies in the HER-2-positive ABC setting [30,50,51,64].…”

Section: Cardiac Safetymentioning

confidence: 99%

HER Story: The Next Chapter in HER-2-Directed Therapy for Advanced Breast Cancer

et al. 2013

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“…A direct comparison of lapatinib and trastuzumab has been done recently (Gelmon et al 2012). ln this phase III trial, 636 therapy-naïve patients with metastatic breast cancer were randomized to receive a taxane-based chemotherapy either with lapatinib or with trastuzumab, each for 24 weeks, following anti-HER2 monotherapy for 4 years or until progressive disease.…”

Section: First-line Treatment In Advanced Breast Cancermentioning

confidence: 99%

Lapatinib

Nölting

Schneider-Merck

Trepel

2014

Recent Results in Cancer Research

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The human epidermal growth factor receptor (HER) family of receptor tyrosine kinases plays an important role in the biology of many cancers. In breast and gastric cancer, and maybe also additional tumor types, HER2 and its homo- or heterodimerization with HER1 or HER3 are essential for cancer cell growth and survival. Breast cancer patients overexpressing HER2 have a poor prognosis, which can be substantially improved upon HER2-targeted therapy using the monoclonal antibody trastuzumab. Lapatinib is a dual tyrosine kinase inhibitor (TKI), blocking HER1 and HER2 tyrosine kinase activity by binding to the ATP-binding site of the receptor's intracellular domain. This results in the inhibition of tumor cell growth. In patients, the drug is relatively well tolerated with mostly low-grade adverse effects. In particular and unlike to trastuzumab, it has very little, if any, adverse effects on cardiac function. In 2007, lapatinib has been approved in combination with capecitabine in patients with advanced HER2-positive breast cancer upon progressive disease following standard therapy with anthracyclines, taxanes, and trastuzumab. In 2010, the approval was extended to the treatment of postmenopausal women with advanced, hormone receptor- and HER2-positive breast cancer, for whom hormonal therapy is indicated. Ongoing and future studies will explore its role in the (neo)adjuvant therapy setting, in further drug combinations as well as in the treatment of HER2-positive tumors other than breast cancer.

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“…In the recently reported interim analysis, 636 pts (525 HER2 centrally confirmed) were included [37]. In the intention to treat analysis, PFS was inferior with lapatinib compared to trastuzumab [hazard ratio (HR) = 1.33; 95% CI 1.06 -1.67; p = 0.01].…”

Section: Lapatinib In the Metastatic Settingmentioning

confidence: 99%

Lapatinib, a TKI Dual Inhibitor of Her1 and Her2 Receptors: Review of the Literature

Lorusso¹,

Marech²,

Giampaglia³

et al. 2012

JCT

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Lapatinib ditosylate (Tyverb ®) is a potent and selective oral dual receptor tyrosine kinase inhibitor (TKI), preventing autophosphorylation of epidermal growth factor receptor (EGFR/ErbB1) and human epidermal growth factor receptor 2 (HER2/ErbB2) intracellular domain. This interference blocks the Ras/Raf MAPKs and PI3K/Akt pathways, that lead to uncontrolled cellular proliferation and survival. After the demonstration of its effectiveness and safety in HER2-overexpressed breast cancer, in 2007 the US Food and Drug Administration (FDA) approved this molecule in combination with capecitabine, in patients with locally advanced or metastatic disease, that progressed after previous treatment with anthracyclines, taxanes and trastuzumab. In 2010, Lapatinib received approval for the treatment of postmenopausal women with hormone receptor positive metastatic breast cancer in combination with letrozole. The most common adverse events (AE) are: anorexia, insomnia, diarrhea and skin rash and mild cardiovascular toxicity. This paper reviews the most important studies on Lapatinib in advanced breast cancer. However, promising results were recently reported on this drug, also in adjuvant setting and in combination with other target drugs, which warrant further investigation for the future.

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Open-label phase III randomized controlled trial comparing taxane-based chemotherapy (Tax) with lapatinib (L) or trastuzumab (T) as first-line therapy for women with HER2+ metastatic breast cancer: Interim analysis (IA) of NCIC CTG MA.31/GSK EGF 108919.

Cited by 49 publications

References 0 publications

HER Story: The Next Chapter in HER-2-Directed Therapy for Advanced Breast Cancer

HER Story: The Next Chapter in HER-2-Directed Therapy for Advanced Breast Cancer

Lapatinib

Lapatinib, a TKI Dual Inhibitor of Her1 and Her2 Receptors: Review of the Literature

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