This randomized phase III trial studies fulvestrant and lapatinib to see how well they work compared to fulvestrant and a placebo in treating postmenopausal women with stage III or stage IV breast cancer that is hormone receptor-positive. Estrogen can cause the growth of breast cancer cells. Hormone therapy using fulvestrant may fight breast cancer by lowering the amount of estrogen the body makes. Lapatinib may stop the growth of breast cancer cells by blocking some of the enzymes needed for cell growth. It is not yet known whether fulvestrant is more effective with or without lapatinib in treating breast cancer.
PRIMARY OBJECTIVES: I. To compare the effect, in terms of progression free survival, of the antiestrogen fulvestrant alone with fulvestrant administered in combination with the dual-kinase inhibitor lapatinib for postmenopausal women with estrogen receptor (ER) and/or progesterone receptor (PgR) positive advanced breast cancer. SECONDARY OBJECTIVES: I. To compare the effects of fulvestrant alone with fulvestrant and lapatinib on other clinical endpoints, including response rate, response and stable disease rate (complete response \[CR\] + partial response \[PR\] + stable disease \>= 6 months), duration of response, overall survival, symptom checklist scores, and toxicity. II. To define predictive markers of clinical activity among women receiving fulvestrant with or without lapatinib. III. To determine if the clinical benefits for combination of hormonal and growth factor inhibitor therapy are most pronounced in women whose tumors express higher levels of ER, epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), phosphorylated protein kinase B (pAkt), and/or phosphorylated mitogen-activated protein kinase 1/2 (pERK1/2). IV. To serologically determine if HER2 extracellular domain (ECD) and EGFR ECD levels can identify patients with a greater likelihood of response and clinical benefit to fulvestrant with or without lapatinib. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive lapatinib ditosylate orally (PO) once daily (QD) on days 1-28 and fulvestrant intramuscularly (IM) on days 1 and 15 of course 1 and on day 1 of each subsequent course. ARM II: Patients receive placebo PO QD on days 1-28 and fulvestrant as in Arm I. In both arms, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months for 2 years and then annually for 3 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
295
University of Arkansas for Medical Sciences
Little Rock, Arkansas, United States
Arroyo Grande Community
Arroyo Grande, California, United States
PCR Oncology
Arroyo Grande, California, United States
Providence Saint Joseph Medical Center/Disney Family Cancer Center
Burbank, California, United States
East Bay Radiation Oncology Center
Castro Valley, California, United States
Progression-free Survival (PFS)
PFS was defined as the interval from study entry until disease progression or death resulting from any cause, which ever occurred first. Progression is defined as a 20% increase in the sum of longest diameter of target lesions (per RECIST criteria).
Time frame: Interval from randomization until disease progression or death, whichever occurs first, assessed up to 5 years
Objective Tumor Response Rate
Response was defined by the Response Evaluation Criteria in Solid Tumors (RECIST). A responding participant had either a Complete Response (disappearance of all target lesions) or Partial Response (30% decrease in sum of longest diameter of target lesions). The response rate of measurable tumors will be estimated with its 95% confidence interval according to treatment arm.
Time frame: Up to 5 years
Overall Survival (OS)
Overall survival was measured as the interval from study entry until death, from any cause, or last contact.
Time frame: Study entry to death or last follow-up, up to 5 years
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Eden Hospital Medical Center
Castro Valley, California, United States
Valley Medical Oncology Consultants-Castro Valley
Castro Valley, California, United States
Bay Area Breast Surgeons Inc
Emeryville, California, United States
Valley Medical Oncology Consultants-Fremont
Fremont, California, United States
Glendale Memorial Hospital and Health Center
Glendale, California, United States
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