Treating postmenopausal women with HER2- and hormone-receptor positive metastatic breast cancer with lapatinib, trastuzumab and aromatase inhibitor

The study evaluated outcomes of lapatinib (Tykerb), trastuzumab (Herceptin), and aromatase inhibitor (AI) in postmenopausal women with human epidermal growth factor receptor 2-positive (HER2+) and hormone receptor-positive (HR+) metastatic breast cancer (MBC). The authors found that the combination was safe and effective in such patients.

HER2 and HR are surface proteins on breast cells. HR helps breast cells grow by accepting female sex hormones. Abnormally high levels of both proteins cause HER2+/HR+ MBC. Both lapatinib (LAP) and trastuzumab (TRAS) inhibit HER2 protein. AIs are a type of hormonal therapy (HT). They reduce female sex hormones in postmenopausal women and stop their HR+ MBC cells from growing.

AIs plus HER2-inhibitors previously showed benefits in HER2+/HR+ MBC. HER2 inhibition by 2 drugs had better outcomes than single HER2-blockade in such patients. However, outcomes of dual-HER2 blockade plus AI are unknown.

The study included 355 postmenopausal women with HER2+/HR+ MBC. 120 women were given LAP, TRAS and AI (LTA group). 117 women received TRAS plus AI (TA group) and 118 received LAP plus AI (LA group). Overall, treatment duration was 53.6 weeks on average.

Progression-free survival (PFS) means how long patients survive without cancer worsening. The average PFS was 11 months in the LTA group, 5.6 months in the TA group, and 8.3 months in the LA group. The LTA group had a 38% lower risk of cancer progression compared to TA. 

The overall response rates (ORR) were 31.7% in the LTA group, 13.7% in the TA group, and 18.6% in the LA group. Response lasted for an average of 14 months in the LTA group, 8.4 months in the TA group, and 11.1 months in the LA group. The average overall survival was 46 months for the LTA group, 40 months for the TA group, and 45.1 months for the LA group.

Most side effects to treatment were mild to moderate in all groups. These included diarrhea, rash, nausea, and nail infection. Rates of stopping treatment due to such events were 3% for LTA, 6% for TA and 9% for LA.

The study concluded that dual HER2-blockade by LTA was safe and effective in postmenopausal women with HER2+/HR+ MBC. 

This study was sponsored by GlaxoSmithKline, the manufacturer of lapatinib.