Paclitaxel, Trastuzumab, and Pertuzumab in the Treatment of Metastatic HER2-Positive Breast Cancer

Inclusion Criteria:

- Age ≥18

- Stage IV HER2 (+) breast cancer.

- Histologically documented HER2 (+) breast cancer as defined as IHC 3+ or FISH
amplification of ≥ 2.0 of primary or metastatic site; results from the local lab are
acceptable. (Optional tumor sample collection from primary or metastatic site may be
obtained for HER2 testing at MSKCC).

- ECOG performance 0 -1 (Appendix A)

- 0-1 prior treatment in the metastatic setting (ie: hormone, chemotherapy, biologic,
targeted agents). Prior anthracycline, paclitaxel, and trastuzumab in the adjuvant
setting are allowed. If the patient has one trastuzumab-based treatment in the
metastatic setting and is given a break (even intermittently) from the partner drug
given with trastuzumab and is continued on trastuzumab alone, this would still be
considered as one treatment. For example, if the patient was given paclitaxel +
trastuzumab and was later continued on trastuzumab alone or then restarted on
paclitaxel + trastuzumab (at the physician's discretion for any reason), the regimen
paclitaxel + trastuzumab followed by trastuzumab alone (or followed by paclitaxel +
trastuzumab again) may be considered as one treatment.

- Measurable or non-measurable disease. Measurable lesions are defined as those that can
be measured accurately in at least one diameter, that is 20 mm using conventional
imaging techniques (including incremental CT) or 10 mm using spiral CT equipment and a
lymph node 15 mm along the short axis. Non-measurable lesions are all other lesions,
including small lesions (longest diameter <10mm pathological a lymph nodes with 10 to
less than 15mm along the short axis, bony metastases, leptomeningeal disease, ascites,
pleural/pericardial effusions, inflammatory breast cancer, lymphangitis
carcinomatosis, and heavily calcified and cystic/necrotic lesions.

- LVEF ≥ 50%

- Hematologic parameters: white blood cell (WBC) count of ≥ 3000/ul, absolute neutrophil
count (ANC) ≥1500/ul, platelets ≥ 100,000/ul, hemoglobin ≥ 10.0 g/dl

- Non-hematologic parameters: bilirubin ≤ 1.5 mg/dl, AST/ALT ≤ 2.5 x upper limit of
normal (ULN), alkaline phosphatase ≤ 5 x ULN.

- Creatinine ≤ 1.5 mg/dl

- Patients with stable and treated brain lesions of a duration of ≥ 2 months may be
enrolled.

Exclusion Criteria:

- History of prior cardiac morbidities within 12 months (unstable angina, myocardial
infarction, CHF, uncontrolled ventricular arrhythmias)

- Prior pertuzumab

- History of prior ≥ G 3 hypersensitivity (HSR) or any toxicity to trastuzumab that
warranted permanent cessation of this antibody

- History of prior ≥ G 3 HSR or any toxicity to paclitaxel warranted permanent cessation
of this chemotherapy

- > G 2 peripheral neuropathy

- Patients with a history of chronic hepatitis B or C should be excluded from the study
as paclitaxel is potentially hepatotoxic

- Pregnant patients