Official Title
A Randomized, Double-Blind, Phase III Trial of Paclitaxel/Trastuzumab/Pertuzumab With Atezolizumab or Placebo in First-Line HER2-Positive Metastatic Breast Cancer
Summary:
This randomized phase III trial studies how well paclitaxel, trastuzumab, and pertuzumab with
or without atezolizumab works in treating patients with breast cancer that has spread to
other parts of the body (metastatic). Drugs used in chemotherapy, such as paclitaxel, work in
different ways to stop the growth of tumour cells, either by killing the cells, by stopping
them from dividing, or by stopping them from spreading. Trastuzumab is a form of "targeted
therapy" because it works by attaching itself to specific molecules (receptors) on the
surface of cancer cells, known as HER2 receptors. When trastuzumab attaches to HER2
receptors, the signals that tell the cells to grow are blocked and the cancer cell may be
marked for destruction by the body's immune system. Monoclonal antibodies, such as
pertuzumab, may interfere with the ability of cancer cells to grow and spread. Immunotherapy
with monoclonal antibodies, such as atezolizumab, may induce changes in body's immune system
and may interfere with the ability of tumour cells to grow and spread. It is not yet known
whether giving paclitaxel, trastuzumab, and pertuzumab with or without atezolizumab may kill
more tumour cells.
Trial Description
Primary Outcome:
- Progression free survival
Secondary Outcome:
- Overall survival
- Overall objective response
- Duration of objective response
- Cumulative incidence of brain metastases
- Frequency of adverse events, including late immune-related toxicities
PRIMARY OBJECTIVE:
-
To determine whether the addition of atezolizumab to a regimen of paclitaxel, pertuzumab,
and trastuzumab will improve the progression-free survival (PFS), as assessed by investigator
using Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria, relative to a
regimen of paclitaxel, pertuzumab, trastuzumab, and placebo in patients with newly documented
HER2-positive measurable metastatic breast cancer.
SECONDARY OBJECTIVES:
-
To determine whether the addition of atezolizumab to a regimen of paclitaxel, pertuzumab,
and trastuzumab will improve the overall survival (OS) relative to a regimen of paclitaxel,
pertuzumab, trastuzumab, and placebo.
- To determine whether the addition of atezolizumab to a regimen of paclitaxel, pertuzumab,
and trastuzumab will improve the overall objective response (OR), assessed by investigator
using RECIST 1.1 criteria, relative to a regimen of paclitaxel, pertuzumab, trastuzumab, and
placebo.
- To determine whether the addition of atezolizumab to a regimen of paclitaxel,
pertuzumab, and trastuzumab will improve PFS, OR, and/or duration of objective response
assessed by retrospective blinded central review using RECIST 1.1 criteria, relative to a
regimen of paclitaxel, pertuzumab, trastuzumab, and placebo.
- To determine whether the addition of atezolizumab to a regimen of paclitaxel, pertuzumab,
and trastuzumab will decrease the incidence of subsequent brain metastases in patients
without known brain metastases at study entry relative to a regimen of paclitaxel,
pertuzumab, trastuzumab, and placebo.
- To determine whether the addition of atezolizumab to a regimen of paclitaxel, pertuzumab,
and trastuzumab will contribute to increased patient-reported fatigue in comparison to a
regimen of paclitaxel, pertuzumab, trastuzumab, and placebo.
- To determine the utility of PD-L1 immunohistochemistry (IHC) staining as a predictive and
prognostic biomarker associated with clinical response, as assessed by investigator using
RECIST 1.1 criteria, to atezolizumab in combination with paclitaxel, trastuzumab, and
pertuzumab.
- To determine the immune-related toxicity profile of the two treatment regimens.
- To determine the cardiac safety profile of the two treatment regimens.
EXPLORATORY OBJECTIVES:
-
To determine whether the addition of atezolizumab to a regimen of paclitaxel, pertuzumab,
and trastuzumab will improve the progression-free survival and overall objective response,
assessed by investigator using immune-modified RECIST (iRECIST) criteria, relative to a
regimen of paclitaxel, pertuzumab, trastuzumab, and placebo.
-
To identify potential biomarkers that can predict benefit from the addition of
atezolizumab in patients with newly documented HER2-positive measurable metastatic breast
cancer treated with a regimen of paclitaxel, pertuzumab, and trastuzumab, and placebo.
- To explore the toxicity profile of the two treatment regimens using patient-reported
symptomatic adverse events in addition to standard adverse event reports.
- To determine the feasibility and added value of frequent assessment of toxicity using
Patient Reported Outcomes (PRO)-Common Terminology Criteria for Adverse Events (CTCAE) with
electronic(e)PRO reporting.
OUTLINE:
Patients are randomized to 1 of 2 arms.
ARM I: Patients receive pertuzumab intravenously (IV) over 30-60 minutes on days 1 and 22,
trastuzumab IV over 30-90 minutes on days 1 and 22, paclitaxel IV over 60 minutes on days 1,
8, 15, 22, 29, and 36, and atezolizumab IV over 60 minutes on days 1 and 22. Cycles for
pertuzumab, trastuzumab and atezolizumab repeat every 6 weeks and treatment with paclitaxel
repeats every 6 weeks for up to 4 cycles in the absence of disease progression or
unacceptable toxicity. Patients may receive additional 3 cycles of paclitaxel in the absence
of progression at the investigator's discretion
ARM II: Patients receive pertuzumab, trastuzumab, and paclitaxel as in Arm I. Patients also
receive placebo IV over 60 minutes on days 1 and 22. Cycles for pertuzumab, trastuzumab, and
placebo repeat every 6 weeks and treatment with paclitaxel repeats every 6 weeks for up to 4
cycles in the absence of disease progression or unacceptable toxicity. Patients may receive
additional 3 cycles of paclitaxel in the absence of progression at the investigator's
discretion.
After completion of study treatment, patients are followed up every 3 months for 3 years and
then every 6 months for 4 years.
View this trial on ClinicalTrials.gov
