Phase 3
Completed N=1,286
Study Comparing Lapatinib (GW572016) And Letrozole Versus Letrozole In Subjects With Advanced Or Metastatic Breast Cancer
Source: ClinicalTrials.gov NCT00073528 ↗Enrolled (actual)
1,286
Serious AEs
19.8%
Results posted
May 2012
Primary outcomePrimary: Number of Participants With Progression Free Survival (PFS) in the Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced or Metastatic Breast Cancer as Assessed by the Investigator — 89; 88 Participants — p=0.019
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Progression Free Survival (PFS) in the Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Advanced or Metastatic Breast Cancer as Assessed by the Investigator |
89; 88 | 0.019 sig |
| PRIMARY Progression Free Survival (PFS) of Participants in the HER2-Positive Population as Assessed by the Investigator |
13.0; 35.4 | 0.019 sig |
| SECONDARY Number of Participants With PFS in the Intent-To-Treat (ITT) Population as Assessed by the Investigator |
476; 413 | — |
| SECONDARY PFS in Participants in the ITT Population as Assessed by the Investigator |
47.0; 51.7 | — |
| SECONDARY Overall Survival in the HER2-Positive Population |
140.3; 144.7 | — |
| SECONDARY Overall Tumor Response (OR) for Participants With Measurable and Non-measurable Disease, Including Bone Scans, in the HER2-Positive Population as Assessed by the Investigator |
14.8; 27.9 | — |
| SECONDARY Number of Participants With Overall Tumor Response (OR) by Stratification Factors With Measurable Disease, Including Bone Scans, in the HER2-Positive Population as Assessed by the Investigator |
14; 31; 0; 0; 12; 24 | — |
| SECONDARY Clinical Benefit (CB) in the HER2-Positive Population as Assessed by the Investigator |
28.7; 47.7 | — |
| SECONDARY Number of Participants With the Indicated Best Response From the Participants With Measurable and Non-measurable Disease, Including Bone Scans, in the HER2-Positive Population as Assessed by the Investigator. |
4; 5; 12; 26; 35; 44 | — |
| SECONDARY Number of Participants With the Indicated Best Response From the Participants With Measurable and Non-measurable Disease, Including Bone Scans, in the ITT Population as Assessed by the Investigator. |
26; 28; 153; 168; 243; 280 | — |
| SECONDARY Number of Participants With the Indicated Time to Response for CR or PR in the HER2-Positive Population as Assessed by the Investigator |
11; 23; 1; 3; 4; 5 | — |
| SECONDARY Duration of Response for the Participants With CR or PR in the HER2-Positive Population as Assessed by the Investigator |
84.4; 47.4 | — |
| SECONDARY Number of Participants With Evidence of Brain Metastases in the HER2-Positive Population |
2; 1 | — |
| SECONDARY Time to Progression (TTP) for the HER2-Positive Population as Assessed by the Investigator |
13.0; 35.4 | — |
| SECONDARY Overall Survival in the ITT Population |
176.3; 170.9 | — |
| SECONDARY Overall Tumor Response (OR) for Participants With Measurable and Non-measurable Disease, Including Bone Scans, in the ITT Population as Assessed by the Investigator |
27.8; 30.5 | — |
| SECONDARY Number of Participants With Overall Tumor Response (OR) by Stratification Factors With Measurable Disease, Including Bone Scans, in the ITT Population as Assessed by the Investigator |
170; 190; 151; 168; 19; 22 | — |
| SECONDARY Clinical Benefit (CB) in the ITT Population as Assessed by the Investigator |
50.6; 55.8 | — |
| SECONDARY Number of Participants With the Indicated Time to Response for CR or PR in the ITT Population as Assessed by the Investigator |
76; 94; 21; 18; 28; 28 | — |
| SECONDARY Duration of Response for the Participants With CR or PR in the ITT Population as Assessed by the Investigator |
72.6; 60.1 | — |
| SECONDARY Number of Participants With Evidence of Brain Metastases From the ITT Population |
4; 6 | — |
| SECONDARY TTP for Participants From the ITT Population as Assessed by the Investigator |
47.0; 51.7 | — |
| SECONDARY Number of Participants Completing the Functional Assessment of Cancer Therapy-breast (FACT-B) Questionnaire at the Scheduled Visits |
605; 605; 460; 476; 350; 382 | — |
| SECONDARY Adjusted Mean Change From Baseline for the FACT-B Total Score Using Observed Data |
1.5; 3.3; 3.8; 1.9; 3.3; 1.4 | — |
| SECONDARY Adjusted Mean Change From Baseline for the Functional Assessment of Cancer Therapy-General (FACT-G) Score Using Observed Data |
1.6; 1.5; 2.2; 0.6; 2.6; 0.9 | — |
| SECONDARY Adjusted Mean Change From Baseline for the Trial Outcome Index (TOI) Score Using Observed Data |
-0.3; 2.7; 3.9; 2.0; 3.3; 0.8 | — |
| SECONDARY Number of Participants Classified as QOL Responders Based on the FACT-B, FACT-G, and TOI Total Scores |
29; 33; 29; 38; 29; 33 | — |
| SECONDARY Number of Participants With Clinical Benefit Categorized by HER2 Fluorescence in Situ Hybridization (FISH) Status |
28; 49; 237; 245; 61; 64 | — |
| SECONDARY Number of Participants With Clinical Benefit Categorized by HER2 ImmunoHistoChemistry (IHC) Intensity |
74; 106; 108; 106; 94; 85 | — |
| SECONDARY Number of Participants With Response in Participants With Baseline Serum HER2 Extracellular Domain (ECD) Baseline Values Greater Than 15 Nanograms Per Milliliter (ng/mL) and 15 ng/mL or Lower |
3; 9; 11; 13; 39; 12 | — |
| SECONDARY Number of HER2-Negative Participants at Baseline With and Without Seroconversion to a Status of HER2 Positive |
323; 140; 52; 219; 99; 119 | — |
| SECONDARY Time to Seroconversion for Participants Who Were HER2 Negative at Baseline But Became HER2 Positive |
NA; 36.1 | — |
| SECONDARY Number of Participants With the Indicated Expression of Tumor by Epidermal Growth Factor Receptor (ErbB1/HER1/EGFR) at Baseline |
513; 522; 43; 45; 17; 12 | — |
Eligibility Criteria
Key inclusion criteria
- Signed informed consent;
- 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.
- Tumors that were ER+ and/or PgR+;
- Post-menopausal female subjects ≥ 18 years of age.
- ECOG Performance Status of 0 or 1;
- Subjects who had archived tumor tissue available to compare tumor response with intra-tumoral expression of ErbB1 and ErbB2.
- 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.
- 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
- Pre-menopausal, pregnant, or lactating;
- Received prior chemotherapy, hormonal therapy, immunotherapy, biologic therapy, or anti-ErbB1/ErbB2 therapy for advanced or metastatic disease;
- 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;
- Used an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of randomized therapy (lapatinib or placebo);
- 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.)
- Subjects with active or uncontrolled infection and/ or with history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure.
Data sourced from ClinicalTrials.gov (NCT00073528). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.