A Study Of PF-05280014 [Trastuzumab-Pfizer] Or Herceptin® [Trastuzumab-EU] Plus Paclitaxel In HER2 Positive First Line Metastatic Breast Cancer Treatment (REFLECTIONS B327-02)

• Biological: PF-05280014
  Concentrate for solution for infusion, sterile vial 150 mg. Initial dose of 4 mg/kg over 90 minutes (depending on tolerability) IV infusion, then 2 mg/kg over 30 to 90 minutes (depending on tolerability) IV infusion until disease progression. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the PF-05280014 regimen may be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
  Other Name: Trastuzumab-Pfizer
• Drug: Paclitaxel
  A nonaqueous solution intended for dilution with a suitable parenteral fluid prior to intravenous infusion. Paclitaxel is available in 30 mg (5 mL), 100 mg (16.7 mL), and 300 mg (50 mL) multidose vials. Each mL of sterile nonpyrogenic solution contains 6 mg paclitaxel. The starting dose of paclitaxel will be 80 mg/m^2 by IV infusion over 60 minutes (duration of infusion may be modified according to local standard of care, if applicable). Provision is made for dose reduction to 70 mg/m^2 and then 60 mg/m^2 as needed. In the absence of disease progression in the judgment of the investigator or prohibitive toxicity, patients will receive treatment with paclitaxel for at least 6 cycles or until maximal benefit of response is obtained, in the judgment of the investigator.
• Biological: Herceptin®
  Concentrate for solution for infusion, sterile vial 150 mg. Initial dose of 4 mg/kg over 90 minutes (depending on tolerability) IV infusion, then 2 mg/kg over 30 to 90 minutes (depending on tolerability) IV infusion weekly until disease progression. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the Herceptin® regimen may be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
  Other Name: Trastuzumab (EU)

• Experimental: PF-05280014
  Interventions:

  • Biological: PF-05280014
  • Drug: Paclitaxel
• Active Comparator: Herceptin®
  Interventions:

  • Biological: Herceptin®
  • Drug: Paclitaxel

• Chen X, Li C, Ewesuedo R, Yin D. Population pharmacokinetics of PF-05280014 (a trastuzumab biosimilar) and reference trastuzumab (Herceptin(®)) in patients with HER2-positive metastatic breast cancer. Cancer Chemother Pharmacol. 2019 Jul;84(1):83-92. doi: 10.1007/s00280-019-03850-1. Epub 2019 May 3. Erratum in: Cancer Chemother Pharmacol. 2019 Sep;84(3):667.
• Pegram MD, Bondarenko I, Zorzetto MMC, Hingmire S, Iwase H, Krivorotko PV, Lee KS, Li RK, Pikiel J, Aggarwal R, Ewesuedo R, Freyman A, Li R, Vana A, Yin D, Zacharchuk C, Tan-Chiu E. PF-05280014 (a trastuzumab biosimilar) plus paclitaxel compared with reference trastuzumab plus paclitaxel for HER2-positive metastatic breast cancer: a randomised, double-blind study. Br J Cancer. 2019 Jan;120(2):172-182. doi: 10.1038/s41416-018-0340-2. Epub 2018 Dec 20.

Inclusion Criteria:

• Histologically confirmed diagnosis of breast cancer.
• Presence of metastatic disease.
• Documentation of HER2 gene amplification or overexpression.
• Available tumor tissue for central review of HER2 status.
• At least 1 measurable lesion as defined by RECIST 1.1.
• Eastern Cooperative Oncology Group status of 0 to 2.
• Left ventricular ejection fraction within institutional range of normal, measured by either two dimensional echocardiogram or multigated acquisition scan.

Exclusion Criteria:

• Relapse within 1 year of last dose of previous adjuvant (including neoadjuvant) treatment (except endocrine therapy) and within 1 year before randomization.
• Prior systemic therapy for metastatic disease (except endocrine therapy).
• Prior cumulative dose of doxorubicin of >400 mg/m2, epirubicin dose >800 mg/m^2, or the equivalent dose for other anthracyclines or derivatives (eg, 72 mg/m^2 of mitoxantrone). If the patient has received more than one anthracycline, then the cumulative dose must not exceed the equivalent of 400 mg/m^2 of doxorubicin.
• Inflammatory breast cancer.
• Active uncontrolled or symptomatic central nervous system metastases.