Researchers from the International Breast Cancer Center (IBCC) have led the PHERGain clinical trial that shows that PET-CT could identify around 40% of patients with localized HER2-positive breast cancer who could be spared preoperative chemotherapy. ”This study could mean, in the near future, the end of chemotherapy in a significant percentage of patients with this type of tumour,” says Dr. José Pérez, first author of the study and deputy director of the IBCC.
The PHERGain clinical trial, published today in the prestigious journal The Lancet Oncology, has been promoted by MEDSIR, a company dedicated to promoting independent clinical research in oncology, and led by Dr. José Pérez, first author of the study, Dr. Javier Cortés,director of the IBCC, and Dr. Antonio Llombart, from the Arnau de Vilanova Hospital in Valencia. It is the first study conducted on patients with localized HER2-positive breast cancer with a strategic and adaptive design, which consists of adapting the treatment to each patient depending on the therapeutic response observed, and is part of a line of research of great importance for improving the treatment and quality of life of these patients, which the researchers of the IBCC have been working on for years. The preliminary results of this study were presented in May 2020 at the 56th congress of the American Society of Clinical Oncology (ASCO).
HER2-positive breast cancer represents 15-20% of all diagnosed breast tumours and is characterized by the expression of a protein called HER2, which increases the aggressiveness and possibility of metastasis of these tumours. Patients diagnosed with localized HER2-positive breast cancer are systematically treated with a combination of chemotherapy and antibodies that act against the HER2 protein.
Thanks to the therapeutic advances that have been made in recent years to treat these tumours, and to the introduction of new anti-HER2 therapies with high antitumour efficacy, the prognosis for these tumours is excellent. The current objective of the scientific community is to find treatment strategies that allow these patients to be treated without the use of chemotherapy. These are known as therapeutic de-escalation strategies, which consist of eliminating unnecessary and toxic treatments, without having a negative impact on the patient’s prognosis. The PHERGain study was carried out in this medical-scientific context.
This phase II clinical trial involved researchers from 45 centres in seven European countries, and included a total of 356 patients with localized HER2-positive breast cancer who were randomized to receive trastuzumab and pertuzumab with chemotherapy (Group A, 71 patients) or without chemotherapy (Group B, 285 patients), respectively. All patients underwent a PET-CT imaging test after two treatment cycles for early observation of the tumour response. The result of this PET-CT scan, and the pathological response achieved, determined the treatment to be followed in the patients included in Group B of the study.
In relation to the findings, Dr. Javier Cortés stressed that “the initial results of the PHERGain clinical trial demonstrate that early assessment of the response to exclusive preoperative treatment with a dual HER2 blockade of trastuzumab and pertuzumab, through the use of PET-CT, is able to identify approximately 40% of patients with localized HER2-positive breast cancer who achieve a pathological complete response without the use of chemotherapy”.
The IBCC is now also leading the PHERGain-2 clinical trial, backed by MEDSIR. This is another important study of therapeutic de-escalation in patients with localized HER2-positive breast cancer which, in addition to treatment with a dual HER2 receptor blockade of trastuzumab and pertuzumab, also integrates treatment with T-DM1, an antibody-drug conjugate with significant antitumour activity in HER2-positive tumours. This new study aims to avoid chemotherapy in an even greater percentage of patients than was achieved in the PHERGain clinical trial.