The combination of lapatinib and letrozole delays the progression of metastatic breast cancer in postmenopausal women ErbB2 +.

The combination of lapatinib and letrozole delays the progression of metastatic breast cancer in postmenopausal women ErbB2 +.

according to a study presented at an international conference on breast cancer

The combination of lapatinib (Tyverb ®) and letrozole (an aromatase inhibitor) as first-line treatment delays the progression of metastatic breast cancer HER2 positive compared with letrozole alone [i], according to a study presented at the 31 San Antonio Breast Cancer Symposium (SABCS).

Lapatinib (Tyverb ®) is available in Spain this month for breast cancer patients with advanced or metastatic ErbB2 + whose tumor has progressed following prior treatment with anthracyclines, taxanes and trastuzumab [ii] for metastatic disease and for which so far there was no other treatment alternative. This drug, GlaxoSmithKline (GSK) is administered to these patients in combination with capecitabine.

The study presented in SABCS EGF30008 is a phase III clinical esnsayo, double-blind, randomized, placebo that enrolled 1286 postmenopausal women with metastatic breast cancer with hormone receptor positive. Some of the patients included in this study expresses the ErbB2 receptor. The study patients received either letrozole 2.5 mg once daily plus 1500 mg of lapatinib, or 2.5 mg of letrozole plus placebo. The first objective was to test the disease-free survival in the subpopulation was also overexpressed the ErbB2 receptor and, as secondary endpoints of progression-free survival in the group of patients. Other secondary endpoints were overall response rate, clinical benefit rate, time to response, duration of it, overall survival, safety and quality of life. Hormone therapy was permitted only in the group receiving adjuvant treatment (1 year before study entry).

The patients experienced 5.2 months of increased survival free of disease progression compared with women treated with letrozole alone (8.2 months vs. 3). Across the group receiving lapatinib with letrozole treatment, irrespective of whether the receptor ErbB2 was overexpressed or not, the median progression-free survival was more than a month with letrozole alone (11.9 months versus 10.9).

The combination of letrozole and lapatinib was safe and no serious adverse effects were identified. Adverse effects of grade 3 / 4 occurred in 2% of patients in both the group receiving the combination as monotherapy and included diarrhea, back pain, fatigue and increased transaminases (ALT and AST).

The growth factor receptors, such as those belonging to the ErbB family, play a key role in growth and cell survival [iii]. The power to talk to these protein receptors is a way to kill tumor cells and tumor growth tackle. About 70% of breast cancers are hormone receptor positive and only one third of them respond to treatment with aromatase inhibitors. Even many of the responsive tumors may become resistant, leading to tumor progression and, ultimately, a fatal outcome [iv]. Recent studies have revealed interactions between hormone receptors and ErbB receptors as major contributors to the development of resistance, and have served as the basic hypothesis for this study [v].

ErbB2 + breast cancer

The HER2 + breast cancer strikes nearly half (44% -48%) of patients younger than 40 years and one quarter of all breast cancer patients [vi] [vii]. It is one of the most aggressive, poor prognosis and therefore at higher risk of recurrence and mortality. About half of patients with metastatic breast cancer ErbB2 + unresponsive to existing therapies so far and the most responsive patients show progression of the disease in the year following the tratamiento4, 5. So far, there were no other therapeutic alternatives for these patients.


Unlike other treatments for this cancer, lapatinb is the first orally administered targeted therapy, allowing patients to take treatment at home. Lapatinib has a novel mechanism of action: it acts from inside the cell, inhibiting both the ErbB1 and ErbB2 receptor, both of growth and proliferation tumoral6, 7. Being able to act from inside the cell, Tykerb will not be affected by any amendments or by the presence of mutations in the extracellular domain of receptor8.


GlaxoSmithKline (GSK)


GSK is a pharmaceutical company engaged in research and development of new cancer treatments that will make profound differences in the lives of patients. GSK has a portfolio of investigational drugs strongest in the oncology sector. The research effort involves collaboration GSK Oncology with more than 160 cancer centers worldwide. GSK is investigating various treatment modalities against cancer, both those focusing on prevention and palliative treatment, chemotherapy and targeted therapies against specific molecular targets.