New results from a study in metastatic breast cancer showed that the combination of Tyverb/Tykerb (lapatinib) plus letrozole as a first line treatment regimen provided a significant improvement in delaying disease progression when compared to treatment with Femara (letrozole) alone.

In the study, women diagnosed with post-menopausal, hormone receptor positive (HR+) and ErbB2 positive metastatic breast cancer experienced a 5.2 month increase in median progression free survival (PFS) compared to women treated with letrozole alone. These data were unveiled at the 31stAnnual CTRC-AACR San Antonio Breast Cancer Symposium.

This double blind, placebo controlled study (EGF30008) included 1,286 post-menopausal women with HR+ breast cancer who were randomised to treatment with lapatinib plus letrozole or to letrozole alone. Letrozole, an aromatase inhibitor (AI), is a recognised therapy in the treatment of HR+ breast cancer. The ErbB2 status of patients was not required for randomisation into the study, however PFS was the primary endpoint in the HR+ and ErbB2 positive patient post study analysis.

Via independent central testing 219 patients were deemed ErbB2 positive.Current treatment regimens for woman who are HR+ and ErbB2 positive include chemotherapy with monoclonal antibody. In the study, women in this patient population who received combination therapy with lapatinib and letrozole experienced a significantly increased median PFS, compared to treatment with letrozole alone (8.2 months versus 3.0 months respectively, HR=0.71, p=0.019)1 - an improvement of 41 per cent.

"The encouraging positive results seen in women who are HR+ and ErbB2 positive shows that the lapatinib and letrozole combination has the potential to become a first-line, oral treatment option for clinicians and patients in this setting in the future, says Paolo Paoletti, SVP Oncology R&D, GSK. "We plan to discuss these data with regulators in the near future."

Results from the intent to treat group (ITT; all patients, irrespective of ErbB2 status) showed that lapatinib plus letrozole provided, on average, an additional month before disease progression compared to letrozole treatment alone (11.9 months versus 10.9 months, HR=0.86, p=0.026). Within the ITT group there was therefore a small subset of HR+ ErbB2 negative women who benefited from this treatment combination and further investigations into this specific group of women are warranted.

The combination of letrozole and lapatinib was manageable, and no new safety issues were identified. Grade 3 / 4 adverse events that occurred in more than two per cent of patients in either the combination arm or monotherapy arm included diarrhoea (9 per cent vs. <1 per cent, respectively); back pain (2 per cent vs. 2 per cent, respectively); fatigue (2 per cent vs. < 1 per cent, respectively); increased ALT (2 per cent vs. <1 per cent, respectively) and increased AST (2 per cent vs. <1 percent, respectively).

Growth factor receptors such as those in the ErbB family play a key role in cell growth and survival. Targeting these protein receptors is a way in which cancer cells can be killed and tumour growth curtailed. Approximately 70 percent of all breast cancer cases are HR+ and only a third of all HR+ tumours respond to first-line treatment with AIs. Furthermore, tumours that initially respond to AIs can become resistant, leading to disease progression and ultimately, patient death. Recent studies have revealed interactions between HR and ErbB receptors as a primary contributor to the development of resistance, and served as the hypothesis basis for this study.