Conditions: Breast Neoplasms
Keywords: Lapatinib Letrozole breast carcinoma breast cancer breast lump HER2 positive metastatic breast cancer breast cancer positive for human epidermal growth factor receptor 2 HER2 breast cancer progression estrogen-receptor positive breast cancer ER
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 1286
Healthy volunteers: no

Brief summary:
This study evaluated and compared the efficacy and tolerability of lapatinib and letrozole, with letrozole and placebo in post-menopausal women with hormone receptor positive (ER positive and/or PgR positive) advanced or metastatic breast cancer, who had not received prior therapy for advanced or metastatic disease.

Detailed description:
Subjects were randomly assigned to receive either lapatinib (1500 mg once daily orally) with letrozole (2.5 mg once daily orally), or letrozole (2.5 mg once daily orally) with placebo (which matched with lapatinib tablet). Randomization was stratified by site of disease (i.e., soft tissue/visceral disease versus bone only disease) and time since prior adjuvant endocrine therapy (\<6 months or ≥ 6 months from discontinuation of adjuvant anti-estrogen therapy (e.g. tamoxifen or raloxifene) or no prior adjuvant antiestrogen therapy). Study therapy was administered daily until disease progression (objective or symptomatic) or withdrawal from therapy (e.g., due to unacceptable toxicity, withdrawal of consent, or other reason). All subjects were to be followed for survival information until death.

On 13 Apr 2015, after the introduction of the Long Term Follow UP (LTFU) phase (per protocol amendment 07), subjects receiving study treatment with lapatinib plus letrozole, or letrozole plus placebo had continued access to this study treatment until the occurrence of one of the following criteria:

* Disease progression (as determined by the Investigator),
* Intercurrent illness that prevented further administration of study treatment
* Drug related AE which was considered by the investigator to warrant permanent discontinuation of study treatment
* The subject decided to withdraw from the study. Investigators collected AEs and/or SAEs related to study participation, until 30 days following study treatment discontinuation. Subjects who were being followed-up for OS but were not taking study medication, were withdrawn from the study.

The study was terminated on 22-Mar-2018 (last subject last visit).

Arms:
arm 1: Letrozole (2.5 mg once daily orally) with Placebo (which matched with Lapatinib tablet) arm 2: Lapatinib (1500 mg once daily orally) with Letrozole (2.5 mg once daily orally)

Interventions: intervention 1: Lapatinib intervention 2: Letrozole intervention 3: Placebo
Intervention descriptions: intervention 1: 1500 mg orally once a day intervention 2: 2.5 mg orally once a day intervention 3: Placebo (which matched with lapatinib tablet)

Protocol document: