Study Comparing Lapatinib (GW572016) And Letrozole Versus Letrozole In Subjects With Advanced Or Metastatic Breast Cancer
Condition: Breast Neoplasms
MeSH terms: Breast Neoplasms
Intervention: Lapatinib; Letrozole; Placebo
Intervention description: 1500 mg orally once a day; 2.5 mg orally once a day; Placebo (which matched with lapatinib tablet)
Intervention MeSH terms: Letrozole; Lapatinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1286.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
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

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.
    

Eligibility criteria:

        Key inclusion criteria

          1. Signed informed consent;

          2. Subjects with histologically confirmed invasive breast cancer with stage IV disease at
             primary diagnosis or at relapse after curative-intent surgery;

               -  Subjects with either measurable or non-measurable disease per Response Evaluation
                  Criteria in Solid Tumors (RECIST).

               -  If the disease was restricted to a solitary lesion, its neoplastic nature was
                  confirmed by cytology or histology.

          3. Tumors that were ER+ and/or PgR+;

          4. Post-menopausal female subjects ≥ 18 years of age.

          5. ECOG Performance Status of 0 or 1;

          6. Subjects who had archived tumor tissue available to compare tumor response with
             intra-tumoral expression of ErbB1 and ErbB2.

          7. Adjuvant therapy with an aromatase inhibitor and / or trastuzumab was allowed;
             however, treatment was to stop more than 1 year prior (>12 months) to the first dose
             of randomized therapy.

          8. Subjects must have ended hormonal replacement therapy (HRT) at least 1 month (30 days)
             prior to receiving the first dose of randomized therapy.

        Key exclusion criteria:

          1. Pre-menopausal, pregnant, or lactating;

          2. Received prior chemotherapy, hormonal therapy, immunotherapy, biologic therapy, or
             anti-ErbB1/ErbB2 therapy for advanced or metastatic disease;

          3. Bisphosphonate therapy for bone metastases was allowed; however, treatment was to be
             initiated prior to the first dose of randomized therapy. Prophylactic use of
             bisphosphonates in subjects without bone disease, except for the treatment of
             osteoporosis, was not permitted;

          4. Used an investigational drug within 30 days or 5 half-lives, whichever is longer,
             preceding the first dose of randomized therapy (lapatinib or placebo);

          5. Subjects with known history of/clinical evidence of CNS metastases or leptomeningeal
             carcinomatosis; and / or subjects on concurrent anti-cancer therapies other than
             letrozole; and / or who have not recovered from toxicities related to prior adjuvant
             therapy (surgery, radiotherapy, chemotherapy etc.)

          6. Subjects with active or uncontrolled infection and/ or with history of uncontrolled or
             symptomatic angina, arrhythmias, or congestive heart failure.