Lead Investigator: Evandro de Azambuja, Institut Jules Bordet
Title of Proposal Research: Metastatic HER2-positive breast cancer treated with docetaxel, trastuzumab, and pertuzumab: the impact of early response on patient survival
Vivli Data Request: 7856
Funding Source: None
Potential Conflicts of Interest: Dr. Evandro de Azambuja reports: Honoraria and advisory board: Roche/GNE, Novartis, Seattle Genetics, Zodiacs, Libbs, Pierre Fabre and Lilly
travel grants: Roche/GNE, GSK/Novartis.
Research grant for his institute: Roche/GNE, AstraZeneca, Novartis, and Servier (outside the submitted work).
Research grants from governments or government agencies: None.
The disclosures will be announced in the research publication.
Dr. Debien reports: Grant from Fondation pour la Recherche Médicale
The disclosures will be announced in the research publication.
Summary of the Proposed Research:
Breast cancer (BC) is still the most frequent female cancer with 1 woman of 8 potentially affected by this disease. Breast cancer tumours are classified according to the expression of three main biomarkers: hormone receptors (estrogen and progesterone receptors) and a protein Human Epidermal growth factor Receptor 2 (HER2). The HER2-positive expression was associated with worse patient survival. Since early 2000, numerous progress has been achieved in HER2-positive BC management, by combining standard chemotherapy with anti-HER2 treatments. Despite the improvement in survival with combinations of anti-HER2 therapies, metastatic BC is still incurable. Since the publication of the CLEOPATRA trial results, the combination of docetaxel, trastuzumab, and pertuzumab is a standard first-line strategy for patients with metastatic HER2-positive BC. The combination improves patients’ outcomes [progression-free survival (PFS) and overall survival (OS)]. However, such efficient treatment could be potentially toxic. Thus, optimising the treatment to reduce global toxicity without wasting efficacy is a major challenge. The initial tumour response, generally assessed after three months of treatment, could be a way to identify patients with improved survival, and in the end, explore the biomarkers related to early treatment response. In clinical trials, the efficacy of study treatment is evaluated based on imaging results. The response evaluation criteria in solid tumors (RECIST) distinguish four subgroups: complete response (CR), partial response (PR) ((≥30% decrease in the sum of diameter of target lesions without new lesions), stable disease (SD) (<20% increase in the sum of diameter of the target lesion or <30% decrease in them, without any new lesions), and progressive disease (PD) (≥20% increase in the sum of diameter of the target lesion and/or new lesions).
We hypothesized that the survival of patients would depend on the strength of the anti-tumour response based on the first tumour evaluation assessment by RECIST. To explore this hypothesis, we will analyze patients’ individual initial responses from CLEOPATRA and PERTAIN trials. Exploring patient-level data from clinical trials allows for having a more homogeneous population.
Requested Studies:
A Phase III, Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of Pertuzumab + Trastuzumab + Docetaxel vs. Placebo + Trastuzumab + Docetaxel in Previously Untreated HER2-Positive Metastatic Breast Cancer
Data Contributor: Roche
Study ID: NCT00567190
Sponsor ID: TOC4129g
A Randomized, Two-Arm, Open-Label, Multicenter Phase II Trial Assessing the Efficacy and Safety of Pertuzumab Given in Combination With Trastuzumab Plus an Aromatase Inhibitor in First Line Patients With HER2-Positive and Hormone Receptor-Positive Advanced (Metastatic or Locally Advanced) Breast Cancer
Data Contributor: Roche
Study ID: NCT01491737
Sponsor ID: MO27775