Tyverb in combination with trastuzumab: safety

Tyverb has a well-established safety profile1-4

Safety in the pivotal study EGF104900 study

The safety of Tyverb in combination with trastuzumab was evaluated in the phase III EGF104900 study.1-3

In this study, 296 HER2+ patients were included, of whom 150 had HER2+ hormone receptor-negative (HR-) metastatic breast cancer.4

The most common adverse events reported were diarrhoea, nausea, rash, fatigue and vomiting.3 The most common serious adverse events were cardiac events experienced by 14 patients, with one fatal cardiac event in the combination arm.3

Adverse events in the safety population of the pivotal EGF104900 study

The five most common adverse events reported by 10% or more of patients treated with Tyverb and trastuzumab (n=149) compared with lapatinib monotherapy* (n=146) in EGF104900 (ITT population) were diarrhoea, nausea, rash, fatigue and vomiting.3

Adverse events for the combination group were mostly resolved without the need for dose modification, and the most common adverse events (≥10% incidence) were of grade 1/2.1,2

Serious AEs were experienced by 38/149 patients in the combination group (26%) and 24/146 in the monotherapy group (16%).2 Ten events in the combination arm and three in the monotherapy arm met the protocol-specific definition for serious cardiac events and there was one fatal cardiac event in the combination arm.2

Most common treatment-related adverse events reported by ≥10% of subjects in the EGF104900 trial

Adapted from European Medicines Agency. Assessment report: Tyverb. 2013.

Serious cardiac events occurred in 7% and 2% of patients receiving lapatinib+trastuzumab (L+T) and lapatinib (L), respectively. The cardiac events observed were comparable in nature and severity to those previously seen with lapatinib monotherapy*.4

Overall, incidence of diarrhoea occurred early in treatment and was transient and manageable.2,4

The incidence of grade 1/2 diarrhoea, the only adverse event with rates significantly different between treatment arms, was higher with the combination therapy (p=0.03); the incidence of grade 3 or higher diarrhoea was similar for both treatment groups (7%).1

Adverse events led to permanent treatment discontinuation in 17 patients (11%) treated with the combination compared with 9 patients (6%) treated with lapatinib monotherapy*.1

Serious adverse events were experienced by 26% of patients in the combination arm and 16% in the lapatinib monotherapy* arm. 14 patients (11 in the combination arm and 3 in the lapatinib monotherapy* arm) experienced cardiac events, of which 13 met the protocol-specific definition for serious cardiac events (10 in the combination arm, 3 in the lapatinib monotherapy* arm).2

The cardiac events observed were comparable in nature and severity to those previously seen with lapatinib.3,4

Further information on the EGF104900 study can be found in the clinical evidence section.

*Lapatinib is not approved for use as a single agent.

Tyverb in combination with trastuzumab: dosing

References: 1. Blackwell K, Burstein H, Storniolo A, et al. Randomized study of lapatinib alone or in combination with trastuzumab in women with ErbB2-positive, trastuzumab-refractory metastatic breast cancer. J Clin Oncol. 2010;28:1124–1130. 2. Blackwell K, Burstein H, Storniolo A, et al. Overall survival benefit with lapatinib in combination with trastuzumab for patients with human epidermal growth factor receptor 2-positive metastatic breast cancer: final results from the EGF104900 study. J Clin Oncol. 2012;30:2585–2592. 3. European Medicines Agency June 2013. Assessment report: Tyverb. EMA/H/C/795/II/22. Available from www.ema.europea.eu (Accessed 4 September 2015). 4. Tyverb® (lapatinib) Summary of Product Characteristics. Camberley, UK: Novartis Europharm Limited; 11 August 2015.