A Study of Herceptin (Trastuzumab) in Combination With 2nd-Line Chemotherapy in Patients With HER2 Positive Metastatic Breast Cancer.

Time to disease progression (TTP) in days was defined as the time from enrollment to objective disease progression (all categories other than objective disease progression was set to be censored including death before progression). Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a nontarget lesion, or the appearance of new lesions. Tumor assessments were performed using computer tomography or magnetic resonance imaging. TTP as assessed by investigator, along with a recalculation done by computer algorithm is presented below. Median time was not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.

Objective response rate (ORR) is defined as the percentage of participants with tumor shrinkage of a predefined amount. It is a combination of complete response (CR) and partial response (PR) and was assessed according to the RECIST criteria 1.0. Complete response refers to the disappearance of all target lesions and all non-target non-measurable lesions. Partial Response refers to an at least 30 percent decrease in the sum of longest diameter of target lesions, taking as reference the baseline sum longest diameter. Objective response rate was not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.

Clinical benefit rate (CBR) was defined as the percentage of participants taking a benefit from the treatments. CBR includes 1) Complete response (CR): disappearance of all target lesions and all non-target non-measurable lesions 2) Partial response (PR) : >=30% decrease in the sum of the longest diameter of target lesions and 3) Stable disease (SD): non-PR and non-progressive disease. It was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST 1.0) and assessed by CT or MRI by the investigator. CBR was also assessed by computer. Clinical benefit rate was not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.

Time to treatment failure is defined as a composite endpoint measuring time (number of days) from enrollment to discontinuation of treatment or change in treatment for any reason, including disease progression, treatment toxicity and death. Median time to treatment failure was not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.

Overall Survival is defined as the time (number of days) between enrollment and the date of death due to any cause. Overall survival was not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.

An adverse event (AE) is any untoward medical occurrence in a participant who is administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect.

Participants in the study were evaluated for the serum glutamic oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT) and alkali phosphatase (ALP) at Visit 1 and final study assessments (Up to 5 years). Serum glutamic oxaloacetic transaminase, Serum glutamic-pyruvic transaminase and Alkali Phosphatase levels were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.

Participants in the study were evaluated for the total bilirubin and serum creatinine. Total Bilirubin and serum creatinine levels were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.

Participants in the study were evaluated for the albumin at Visit 1 and Final study assessments. Albumin levels were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.

Participants in the study were evaluated for the biochemical safety laboratory parameters urea, sodium and potassium. Urea, sodium and potassium levels were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.

Participants in the study were evaluated for the Hemoglobin up to 5 years. Hemoglobin levels were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.

Participants in the study were evaluated for the total leukocytes up to 5 years. Total leukocytes counts were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.

Participants in the study were evaluated for the Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes at Visit 1 and final study assessments.

Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes counts were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.

Participants in the study were evaluated for the platelets at Visit 1 and final study assessments. Platelet counts were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.

Left ventricular ejection fraction (LVEF) is a measure of the percent of blood ejected from the ventricle in one heartbeat. It is a measure of cardiac function and was assessed by echocardiogram or multigated angiogram at Visit 0 [Screening period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years).