Tyverb in combination with an aromatase inhibitor

Tyverb in combination with an aromatase inhibitor has demonstrated efficacy in the first-line treatment of HER2+ hormone receptor positive (HR+) metastatic breast cancer in patients not intended for chemotherapy.1

The efficacy of Tyverb in combination with letrozole is clearly demonstrated by the results of the EGF30008 study, which show that in appropriate patients, the combination of Tyverb plus the aromatase inhibitor (AI) provides an effective chemotherapy-free treatment option.1

Effects on progression-free survival

In postmenopausal women with HER2+ HR+ metastatic breast cancer, Tyverb in combination with letrozole significantly increases progression-free survival (PFS) compared with letrozole plus placebo.1,2 The addition of Tyverb to letrozole increased median PFS by 5.2 months in the HER2+ HR+ population (8.2 months vs. 3.0 months, respectively), and led to a significant (29%) reduction in the risk of progression compared with letrozole plus placebo (hazard ratio: 0.71, 95% confidence interval 0.53–0.96; P=0.019).1,2

Tyverb in combination with letrozole significantly increased PFS compared with letrozole plus placebo1

HR=hazard ratio; CI=confidence interval. Adapted from Johnston S, Pippen J Jr, Pivot X, et al. J Clin Oncol. 2009;27:5538–5546.

These data demonstrate the efficacy of an oral, chemotherapy-free regimen of Tyverb in combination with letrozole in patients with HER2+ HR+ metastatic breast cancer not currently intended for chemotherapy.1,2

Effects on overall survival and secondary endpoints

At the time of the final PFS analysis (with median follow-up of 2.64 years), the overall survival data were not mature and there was no significant difference between treatment groups in the HER2+ population. This lack of a significant difference in overall survival data has not changed with additional follow-up (>7.5 years median follow-up time).3

Analysis of response rates revealed that the overall response rate and clinical benefit rate were significantly improved with the addition of Tyverb to letrozole.1,2

Selected secondary endpoints for the HR+/HER2+ population

  Lapatinib plus letrozole (n=111) Letrozole plus placebo (n=108) Odds ratio (95% CI); P-value
Overall response rate (%) 28 15 0.4 (0.2–0.9); P=0.021*
Complete response (%) 5 4 NR
Partial response (%) 23 11 NR
Stable disease for at least 6 months (%) 20 14 NR
Clinical benefit rate (%) 48 29 0.4 (0.2–0.8); P=0.003*
*Response rates were compared using stratified Fisher’s exact test. CI=confidence interval; NR=not reported. Adapted from Johnston S, Pippen J Jr, Pivot X, et al. J Clin Oncol. 2009;27:5538–5546.

Tyverb in combination with an AI: safety

Reference: 1. Johnston S, Pippen J Jr, Pivot X, et al. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol. 2009;27:5538–5546. 2. Schwarzberg L, Franco S, Florance A, et al. Lapatinib plus letrozole as first-line therapy for HER2+ hormone-receptor-positive metastatic breast cancer. Oncologist. 2010;15:122–129. 3. Tyverb® (lapatinib) Summary of Product Characteristics. Camberley, UK: Novartis Europharm Limited; 11 August 2015.