PETRA: PErtuzumab and Trastuzumab Biosimilars Real Life Association for the First Line Treatment of HER2-positive Metastatic Breast Cancer, an Observational Prospective Multicenter Study

Study Overview
=================
Brief Summary
-----------------
Currently there are five trastuzumab biosimilars approved by EMA (Ogivri® Mylan , Herzuma® Biogaran, Ontruzant® MSD, Trazimera® Pfizer, and Kanjinti® Amgen) for the treatment of HER2-positive breast cancer. EMA's approvals were obtained on phase I pharmacokinetic equivalence trials and phase III clinical trials based on efficacy primary endpoints in the neoadjuvant setting and on Overall Response Rate in metastatic setting. Safety was a secondary endpoints in these trials. Phase III pivotal trials compared trastuzumab biosimilars to Herceptin® in combination with chemotherapy in the neoadjuvant setting and in the metastatic setting. The trials were designed before the approval of pertuzumab (in the neoadjuvant and metastatic settings). Thus, there is no available prospective data on the safety and efficacy of trastuzumab biosimilars in combination with pertuzumab. A biosimilar compound can obtain an extrapolation of its indications to those of the reference biological product since bio-similarity has been demonstrated (ie pharmacokinetic equivalence and clinical studies in the most sensitive indications). To date, the use of trastuzumab biosimilar in combination with pertuzumab is allowed, but this combination is not supported by neither scientific evidence nor clinical guidelines. PETRA aims at evaluate the efficacy and safety of the combination of pertuzumab and a trastuzumab biosimilar in real life.

Official Title
-----------------
PETRA: PErtuzumab and Trastuzumab Biosimilars Real Life Association for the First Line Treatment of HER2-positive Metastatic Breast Cancer, an Observational Prospective Multicenter Study

Conditions
-----------------
HER-2 Positive Breast Cancer

Intervention / Treatment
-----------------
* Other: Efficacy of the Pertuzumab-Trastuzumab combination


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically confirmed Patients ≥ 18 years-old with non-operable, locally advanced, or metastatic HER-2 positive breast cancer Docetaxel, Paclitaxel or Vinorelbine-based chemotherapy administred in combination with any trastuzumab biosimilar and with pertuzumab for the first-line treatment of the non-operable, locally advanced or metastatic HER-2 positive breast cancer. WHO Performance status 0-2 Measurable or non-measurable (but radiologically evaluable) disease as per modified Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Adequate cardia function at baseline defined by a left ventricular ejection fraction of 50% or more within 2 months before treatment start Adequate baseline organ function, evidenced by the following laboratory results within 2 months before treatment start: Hemoglobin ≥ 9 g/dL Absolute neutrophil count (ANC) ≥ 1500/mm3 Platelet count ≥ 100,000/mm3 Total bilirubin ≤ 1.5 upper limit of normal (ULN), or total bilirubin ≤ 3.0 × ULN in patients with documented Gilbert's Syndrome. Glomerular Filtration Rate (GFR) ≥ 30 ml/min according to MDRD formula or CKD-EPI formula or Cockcroft and Gault formula SGOT (AST), SGPT (ALT) and alkaline phosphatase ≤ 5 × ULN Patient's consent to data collection Exclusion Criteria: Prior exposure to trastuzumab in the metastatic setting, patients may have received adjuvant or neoadjuvant trastuzumab and/or pertuzumab with an interval of at least 12 months between completion of the adjuvant or neoadjuvant anti-HER2 therapy and the diagnosis of metastatic breast cancer. History of allergic reactions attributed to compounds of chemical or biological composition similar to trastuzumab, pertuzumab, or to chemotherapy components Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (including known HIV, active hepatitis B and/or hepatitis C infection), symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or uncontrolled diabetes

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Efficacy of the Pertuzumab-Trastuzumab combination|The efficacy of the pertuzumab in combination with one of the biosimilars of Trastuzumab will be estimated by measuring the PFS at 6 months after the beginning of the treatment.|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS-R | The primary end-point is the 6 months PFS-R. It will be defined as the proportion of included patients who achieve complete response (CR), partial response (PR) or stable disease (SD) at 6 months after the beginning of the treatment. | 6 months after inclusion |