GlaxoSmithKline announced today that the European Commission has granted an additional indication for Tyverb™ (lapatinib) to be used in combination with trastuzumab. This combination is indicated for adult patients with breast cancer whose tumours overexpress HER2 (ErbB2), with hormone receptor-negative (HR-) metastatic disease that has progressed on prior trastuzumab therapy(ies) in combination with chemotherapy.[1]

“Today’s announcement is important for women with this specific type of metastatic breast cancer, who will have now a new treatment option. The combination of Tyverb™ and trastuzumab, which is chemotherapy-free, has the potential to make a positive impact on the care and survival of these patients,” said Paolo Paoletti, President, GlaxoSmithKline Oncology.

The combination was evaluated in the EGF104900 trial, a randomised, open-label, Phase III study of lapatinib + trastuzumab versus lapatinib monotherapy in patients with HER2-positive metastatic breast cancer whose disease had progressed on a trastuzumab-containing regimen.^[2]a The primary endpoint of the trial was progression-free survival (PFS), with overall survival (OS) as the secondary endpoint.²

The authorisation for the new indication is based on overall survival (OS) results in the HER2-positive, HR-negative metastatic breast cancer population within the EGF104900 trial. This post-hoc subgroup analysis showed that:³

• The combination of lapatinib + trastuzumab was associated with an 8.3 month increase in median OS versus lapatinib monotherapy (17.2 months vs. 8.9 months; n=150; HR=0.62; 95 per cent Confidence Interval 0.42, 0.90).¹

Please note that lapatinib is not licensed for use as a monotherapy in Europe or elsewhere.

Within the EGF104900 trial, the incidence of AEs was similar in both treatment groups (94 per cent vs. 90 per cent). The most frequent adverse reactions (> 25 per cent) during the trial were diarrhoea and nausea. Additional adverse events which affected > 10 per cent of patients included fatigue, vomiting, rash, dyspnoea, anorexia and headache. Serious adverse events, including diarrhoea, decreased cardiac function and hepatobiliary disorders, were experienced by 26 per cent of patients.¹

Adverse events led to treatment discontinuation in 17 patients (11 per cent) treated with lapatinib + trastuzumab compared with nine patients (6 per cent) treated with lapatinib monotherapy. In total, six patients had fatal serious adverse events; of these, one – probable but unconfirmed pulmonary embolism in the combination therapy arm – was considered to be related to study treatment. There was an increased incidence of cardiac toxicity, but these events were comparable in nature and severity to those reported from the lapatinib clinical programme. These data are based on exposure to this combination in 149 patients in the pivotal trial.¹