A study to avoid chemotherapy in patients with early HER-2+ breast cancer

MEDSIR, a global company dedicated to independent clinical research in oncology, has initiated the PHERGain II clinical trial to demonstrate that in patients with HER2-positive early breast cancer with a good prognosis, a chemotherapy-free therapeutic approach can be as effective as the current standard of care, which involves the use of this generally more toxic treatment.

The PHERGain II study's goal is to find an effective therapeutic strategy that can reduce the use of chemotherapy and improve the quality of life of patients without compromising the clinical effectiveness of their treatment. It is also aligned with one of the top priorities in cancer research according to the associations of reference such as the American Society of Clinical Oncology (ASCO): that clinical investigation in oncology prioritizes the reduction of toxicity associated with the treatment of cancer.

“Given the side effects and the impact of chemotherapy on the quality of life of patients with early breast cancer, it is advisable to find a new therapeutic strategy that allows dispense with traditional systemic chemotherapy in those patients who can achieve a similar response with a less toxic treatment”, explained Dr. Antonio Llombart, head of the Medical Oncology Service at the Arnau de Vilanova Hospital (Valencia) and principal investigator of the study.

HER-2+ breast cancer is a type of cancer with a high presence of human epidemic growth factor receptor 2 (HER2), a protein that promotes the growth of cancer cells. When these tumors are found early - before they spread to other areas of the body - they are removed by surgery and treated with therapies aimed at blocking HER2. However, even in patients with a good prognosis, the combination with chemotherapy is still part of the standard treatment to prevent the tumor from coming back after surgery.

For these patients, there is great interest in exploring a combination or optimized sequence of drugs targeting HER2 that eliminates the need for chemotherapy without affecting the clinical benefit of the treatment, which could positively impact their quality of life.

In the PHERGain-II trial, patients will be given preoperative treatment with trastuzumab and pertuzumab, aimed at blocking HER2, without chemotherapy. MRI will scan tumors before and after treatment to determine if the pathological response level after treatment can be predicted by non-invasive tumor imaging. After surgery, depending on the response to therapy with trastuzumab and pertuzumab, treatment with the same combination of drugs or with T-DM1 (another HER2 blocking drug) will be continued, reserving the use of chemotherapy only to those patients who have responded worse to preoperative treatment and who therefore have a worse prognosis.

The earlier PHERGain-I clinical trial has already explored the potential of a chemotherapy-free treatment approach in patients with HER2+ early breast cancer. The results presented at the last ASCO annual meeting were encouraging, since a significant number of patients had a complete pathological response (that is, total absence of signs of cancer at the time of surgery) after receiving preoperative treatment without chemotherapy.

"Although this new therapeutic approach will not allow all patients to dispense with chemotherapy, it opens the door for us to design new ways to reduce the toxicity of antitumor therapies based on the response of the tumor to preoperative treatment", explained Dr. Llombart. In this way, it would be possible to determine those patients in whom targeted therapy alone can achieve results similar to those obtained with the administration of targeted therapy plus chemotherapy, which is the norm today.

To confirm that this strategy is completely effective and to be able to implement it in routine clinical practice, the investigators will carry out a three-year follow-up of these patients to determine their evolution and detect if the relapse rate is equivalent to that obtained through the use of chemotherapy.

A total of 393 patients from 70 health centers in Spain, France, Germany, the United Kingdom, and Italy will participate in the PHERGain-II study.