A Multicenter Randomized Phase III Study to Compare the Combination Trastuzumab and Capecitabine, With or Without Pertuzumab, in Patients With HER2-Positive Metastatic Breast Cancer That Have Progressed After One Line of Trastuzumab-Based Therapy in the Metastatic Setting (PHEREXA)
Overview
- Phase
- Phase 3
- Intervention
- Trastuzumab
- Conditions
- Breast Cancer
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 452
- Locations
- 190
- Primary Endpoint
- Progression Free Survival (Independent Assessment)
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
This randomized, two-arm study evaluated the efficacy and safety of a combination of trastuzumab and capecitabine with or without pertuzumab in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. The study population consisted of female patients, whose disease had progressed during or following previous trastuzumab therapy for metastatic disease. All patients in Arm A and Arm B received trastuzumab (8 mg/kg iv as loading dose and then 6 mg/kg iv every 3 weeks thereafter) and capecitabine oral twice daily for 14 days every 3 weeks (1250 mg/m2 twice daily in Arm A and 1000 mg/m2 twice daily in Arm B). In addition, patients in Arm B received pertuzumab (840 mg iv as loading dose and then 420 mg iv thereafter) every 3 weeks. Study treatment continued until disease progression or unacceptable toxicity.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Adult female patients \>/=18 years of age
- •Metastatic HER2 positive breast cancer
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Disease progression during or following trastuzumab-based therapy for 1st line metastatic breast cancer (trastuzumab must have been part of the last prior treatment regimen)
- •Prior treatment with taxane-containing regimen
- •Left ventricular ejection fraction (LVEF) \>/=50 percent
- •For women of childbearing potential agreement to use highly effective non-hormonal form of contraception or two effective forms of non-hormonal contraception by patient and/or partner. Contraception must continue for duration of study treatment and for at least 6 months after last dose of study drug treatment
Exclusion Criteria
- •Prior treatment with pertuzumab or capecitabine
- •Concurrent treatment with other experimental drug
- •Concurrent immunotherapy or anticancer hormonal therapy
- •Serious concurrent disease (e.g. active infection, uncontrolled hypertension, cardiovascular disease)
- •Central nervous system (CNS) metastases, which are not well controlled
- •History of exposure to anthracycline cumulative dose equivalent to 360mg/m2
- •History of congestive heart failure of any New York Heart Association criteria, or serious cardiac arrhythmia requiring treatment
- •History of myocardial infarction within 6 months prior to randomization
- •History of LVEF decline to below 50% during or after prior trastuzumab therapy or other cardiac toxicity during previous trastuzumab treatment that necessitated discontinuation of trastuzumab
- •History of another cancer which could affect compliance or result interpretation
Arms & Interventions
A: Capecitabine + Trastuzumab
Intervention: Trastuzumab
A: Capecitabine + Trastuzumab
Intervention: Capecitabine
B: Capecitabine + Trastuzumab + Pertuzumab
Intervention: Capecitabine
B: Capecitabine + Trastuzumab + Pertuzumab
Intervention: Pertuzumab
B: Capecitabine + Trastuzumab + Pertuzumab
Intervention: Trastuzumab
Outcomes
Primary Outcomes
Progression Free Survival (Independent Assessment)
Time Frame: Tumor assessments every 9 weeks from randomization until Week 27, then every 12 weeks thereafter, until IRF-determined PD, initiation of alternative anticancer medication, or death (up to 5.5 years).
Progression Free Survival (PFS) was defined as the time from randomization to first documented disease progression (PD), as determined by an Independent Review Facility (IRF) using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. IRF review of tumor assessment ceased after the primary PFS analysis. The primary endpoint was analyzed after approximately 337 IRF-assessed PFS events were observed.
Secondary Outcomes
- Overall Survival (OS) Rate Based on a 2-year Truncated Analysis(From randomization until death from any cause (up to 2 years))
- Overall Survival (OS)(From randomization until death from any cause (up to 7.5 years).)
- Investigator Assessment Progression-Free Survival (PFS)(Tumor assessments every 9 weeks from randomization until Week 27, then every 12 weeks thereafter, until IRF-determined PD, initiation of alternative anticancer medication, or death (up to 7.5 years).)
- Time to Progression (TTP) Based Upon Independent Review Facility (IRF) Assessment(Tumor assessments every 9 weeks from randomization until Week 27, then every 12 weeks thereafter, until IRF-determined PD, initiation of alternative anticancer medication, or death (up to 5.5 years).)
- Time to Treatment Failure (TTF) Based Upon Independent Review Facility (IRF) Assessment(Tumor assessments every 9 weeks from randomization until Week 27, then every 12 weeks thereafter, until IRF-determined PD, initiation of alternative anticancer medication, or death (up to 5.5 years).)
- Overall Objective Response Rate (ORR)(Tumor assessments every 9 weeks from randomization until Week 27, then every 12 weeks thereafter, until IRF-determined PD, initiation of alternative anticancer medication, or death (up to 5.5 years).)
- Clinical Benefit Rate (CBR)(Tumor assessments every 9 weeks from randomization until Week 27, then every 12 weeks thereafter, until IRF-determined PD, initiation of alternative anticancer medication, or death (up to 5.5 years).)
- Duration of Objective Response(Tumor assessments every 9 weeks from randomization until Week 27, then every 12 weeks thereafter, until IRF-determined PD, initiation of alternative anticancer medication, or death (up to 5.5 years).)