A study to compare the safety and efficacy of an aromatase inhibitor in combination with lapatinib, trastuzumab or both for the treatment of hormone receptor positive, HER2+ metastatic breast cancer (MBC).
This Phase III, multicenter, open-label study randomized subjects to one of the three treatment arms: 1. Treatment group A: lapatinib 1000 mg PO once daily + trastuzumab (loading dose of 8 mg/kg) followed by the maintenance dose of 6 mg/kg IV q3weeks + an AI (either letrozole, anastrozole, or exemestane) of Investigator's choice PO once daily. 2. Treatment group B: trastuzumab (loading dose of 8 mg/kg) followed by maintenance dose of 6 mg/kg IV q3weeks + an AI (either letrozole, anastrozole, or exemestane) of Investigator's choice PO once daily. 3. Treatment group C: lapatinib 1500 mg PO once daily + an AI (either letrozole, anastrozole, or exemestane) of Investigator's choice PO once daily. Treatment continued until disease progression, death, or unacceptable toxicities, whichever came first. Subjects who discontinued study treatment for reasons other than disease progression were followed-up every 12 weeks until disease progression or death, until the start of post-study treatment anti-cancer therapy (including radiotherapy and surgery), withdrawal of consent, or lost to follow-up, whichever came first.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
369
1000 mg by mouth once a day
Loading dose of 8 mg/kg IV followed by the maintenance dose of 6 mg/kg IV every 3 weeks (q3weeks)
Aromatase inhibitor (either letrozole, anastrozole, or exemestane) of investigator's choice given by mouth once daily
Progression Free Survival (PFS) Events in Lapatinib + Trastuzumab + Aromatase Inhibitor (AI) vs. Trastuzumab + Aromatase Inhibitor (AI)
The Number of Participants with Progression free survival (PFS) events in the Lapatinib + Trastuzumab + Aromatase Inhibitor (AI) arm vs. Trastuzumab + Aromatase Inhibitor (AI) arm was based on assessments by the Investigator.
Time frame: From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up approximately 5 years
Median Kaplan Meier Estimates for PFS in Lapatinib + Trastuzumab + Aromatase Inhibitor (AI) vs. Trastuzumab + Aromatase Inhibitor (AI)
Progression free survival (PFS) was defined as the interval of time between the date of randomization and the earliest date of disease progression (with radiological evidence) or death from any cause, or to the date of censor. Disease progression was based on assessments by the Investigator.
Time frame: From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up approximately 5 years
Progression Free Survival (PFS)
Progression free survival (PFS) was defined as the interval of time between the date of randomization and the earliest date of disease progression (with radiological evidence) or death from any cause, or to the date of censor. Disease progression was based on assessments by the Investigator.
Time frame: From date of randomization until date of progression or date of death from any cause, whichever comes first, assessed up approximately 11 years
Overall Survival (OS)
The Number of Participants with Overall Survival (OS) events was based on assessments by the Investigator.
Time frame: From date of randomization until date of death from any cause, assessed up approximately 11 years
Overall Response Rate (ORR)
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1500 mg by mouth once daily
Novartis Investigative Site
Hollywood, Florida, United States
Novartis Investigative Site
Augusta, Georgia, United States
Novartis Investigative Site
Germantown, Tennessee, United States
Novartis Investigative Site
Tacoma, Washington, United States
Novartis Investigative Site
Berazategui, Buenos Aires, Argentina
Novartis Investigative Site
Capital Federal, Buenos Aires, Argentina
Novartis Investigative Site
Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina
Novartis Investigative Site
Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina
Novartis Investigative Site
La Plata, Buenos Aires, Argentina
Novartis Investigative Site
Viedma, Río Negro Province, Argentina
...and 100 more locations
Overall Response Rate (ORR) was defined as the proportion of participants achieving either a Complete Response (CR) or Partial Response (PR). The ORR was calculated from the Investigator's assessment of response based on RECIST 1.1. Subjects with an unknown or missing response were treated as non-responders; i.e. they were included in the denominator when calculating the percentages. Subjects who do not have measurable disease contributed to the Response Rate based analyses, for the evaluation of CR, SD and PD.
Time frame: Up approximately 11 years
Clinical Benefit Rate (CBR)
Clinical Benefit Rate (CBR) was defined as the percentage of patients with evidence of Complete Response (CR), Partial Response (PR), or maintaining Stable Disease (SD) for at least 6 months while on study, according to the investigator assessment of response per RECIST 1.1 criteria.
Time frame: Up approximately 11 years
Time to Response
Time to Response (TTR) was defined as the time from randomization to the earliest date of Complete Response (CR) or Partial Response (PR)
Time frame: From date of randomization until the earliest date of Complete Response (CR) or Partial Response (PR), assessed up approximately 11 years
Duration of Response (DoR)
Duration of Response (DOR) was defined as the duration between the date of first documented Complete Response (CR) or Partial Response (PR) and the date of first documented sign of Progressive Disease or Death, or to the date of censor.
Time frame: From first documented evidence of CR or PR (the response prior to confirmation) until time of documented disease progression or death due to any cause, whichever comes first, assessed up approximately 11 years
Mean Change in the Quality of Life (QoL) Status Relative to Baseline FACT-B Overall and Subscale Scores at Last On Treatment Assessment
Quality of life was assessed using the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire. It is a 37-item (27 general questions and 10 breast cancer specific questions) self-reporting instrument consisting of 5 dimensions: physical well-being (PWB), social well-being (SWB), emotional well-being (EWB), functional well-being (FWB), and a breast cancer subscale (BCS). The followings were the score ranges for each self-reporting subscale: • PWB : 0-28 • SWB : 0-28 • EWB : 0-24 • FWB : 0-28 • BCS : 0-40 FACT-B Total Outcome Index (TOI) = PWB + FWB + BCS (range:0 - 96) FACT-B Total Score = PWB + SWB + EWB + FWB + BCS (range:0-148) FACT-G Total Score = PWB + SWB + EWB + FWB (range:0-108). For all the FACIT scales and symptom indices, the higher the score the better QoL
Time frame: Day 1 (pre-dose), up approximately 11 years