Phase II Lapatinib Plus Nab-Paclitaxel As First And Second Line Therapy In her2+ MBC

Inclusion Criteria

A subject was eligible for inclusion in this study only if all of the following criteria apply:

• Subjects must have histologically confirmed invasive breast cancer with Stage IV disease at primary diagnosis or at relapse after curative-intent surgery. Where the disease was restricted to a solitary lesion, the neoplastic nature of the lesion should have been confirmed by cytology or histology.
• Documented amplification of ErbB2 3+ by immunohistochemistry or a positive score (>2.2) by FISH using a local laboratory result (which was considered sufficient in this study with no further verification by a central laboratory).
• Subjects must have received no more than one prior chemotherapeutic regimen in the metastatic setting.
• If a taxane had been administered in the neoadjuvant, adjuvant or metastatic setting, progression must have occurred ≥12 months after completion of this treatment.
• Prior therapy with radiation for this breast cancer population was permitted if it was administered in the neoadjuvant or adjuvant non metastatic setting. Radiotherapy given in the metastatic setting, prior to initiation of study medication, was allowed to a limited area (e.g., palliative therapy and involving less than 25% of bone marrow), if it was not the sole site of disease. Subjects must have completed radiation treatment and recovered from all acute radiation treatment related toxicities (e.g., bone marrow suppression) prior to commencement of combination treatment.
• The subject must have received all prior chemotherapy treatment at least 4 weeks prior to enrollment in this study and must have recovered from all related toxicities. Subjects who have received weekly dose of prior chemotherapy e.g. gemcitabine or capecitabine may enroll 2 to 3 weeks after cessation of treatment provided that they have recovered from all related toxicities.
• Prior therapy with trastuzumab in the neoadjuvant, adjuvant or metastatic setting was permitted. The subject must have received all prior trastuzumab treatment at least 4 weeks prior to enrollment in this study and must have recovered from all related toxicities.
• Prior endocrine therapy was permitted in the neoadjuvant or adjuvant or metastatic setting. The subject must have received all prior endocrine treatment at least 1 week prior to enrollment in this study and must have recovered from all related toxicities.
• Prior diagnosis of cancer was allowed as long as the subject was free of disease for 5 years. Subjects with completely resected basal or squamous cell skin cancer, thyroid cancer or successfully treated cervical carcinoma in-situ were allowed if it had been 1 year or greater since definitive surgery.
• Subjects must have had measurable disease, according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines; defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter [LD] to be recorded) by mammogram, ultrasound or physical exam [Therasse, 2000].
• Subjects with liver metastases or stable chronic liver disease were permitted into the study.
• Women ≥18 years of age:
• Non-child-bearing potential (i.e., women with functioning ovaries who had a current documented tubal ligation or hysterectomy, or women who were postmenopausal); or
• Child-bearing potential (i.e., women with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility). This category included women with oligomenorrhoea (severe), women who were perimenopausal and young women who had begun to menstruate. These subjects must provided a negative serum pregnancy test at Screening and agree to 1 of the following:
• Complete abstinence from intercourse from 2 weeks prior to administration of the first dose of study medication until 5 days after the final dose of study medication; or
• Consistent and correct use of one of the following acceptable methods of birth control:
• Male partner who was sterile p