PHERGain Trial Shows Promise for Chemotherapy-Free Strategy for HER2-Positive Early Breast Cancer
In a groundbreaking clinical trial, MEDSIR has announced the positive outcomes of the PHERGain trial, demonstrating the potential for a chemotherapy-free treatment approach for a subset of patients with HER2-positive early breast cancer. The trial used an adaptive study design that represents a significant advancement in tailoring treatment strategies, focusing on neoadjuvant/adjuvant therapy. The trial's results, presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, have revealed remarkable success rates 3 years after surgery in preventing cancer recurrence in all patients and reducing the need for chemotherapy for a significant subset.
What is the PHERGain Trial?
The PHERGain trial, sponsored by MEDSIR, involved 356 early-stage HER2-positive breast cancer patients from seven European countries, making it a robust and comprehensive study. Led by esteemed scientific investigators Dr. Javier Cortés, Dr. Antonio Llombart-Cussac, and Dr. José Pérez, the trial aimed to assess the feasibility of a chemotherapy-free approach using a dual HER2 blockade with trastuzumab and pertuzumab. The trial employed an adaptive design, tailoring treatment based on patients' therapeutic response observed through positron emission tomography (PET) and pathologic complete response (pCR).
PHERGain Achieved Positive Results
The first primary endpoint of the trial was to evaluate the pCR rate in patients with PET response, which yielded positive results previously published in Lancet Oncology in 2021. The second primary endpoint, focusing on the 3-year invasive disease-free survival in all patients assigned to group B, has now been presented at the ASCO congress. The results are highly encouraging. More than 95% of patients who followed the chemotherapy de-escalation strategy based on the adaptive design remained cancer-free after three years of follow-up from breast cancer surgery. Notably, approximately 30% of these patients successfully avoided chemotherapy, while still maintaining an impressive 99% cure rate after three years of follow-up.
An Adaptive Approach Could Mean Less Chemotherapy
The trial employed an adaptive design, tailoring treatment based on patients' therapeutic response observed through PET and pCR. Study participants were randomly assigned to the standard of care (chemotherapy in combination with trastuzumab and pertuzumab; Group A) or an adaptive treatment with the intent to treat without chemotherapy and based on the individual’s patient response to trastuzumab and pertuzumab (Group B). The treatment response was monitored using PET scans (after 2 cycles of treatment) and pCR (after surgery). Those patients from Group B that responded to the first two cycles of treatment (i.e., the tumor shrunk as shown by PET scan) remained on that regimen without chemotherapy, whereas those not responding were switched to receive chemotherapy in combination with trastuzumab and pertuzumab.
Following surgery, PET responders were evaluated to determine if patients had achieved a pCR. PET responders with a pCR continued with the chemotherapy-free treatment whereas PET responders with no pCR had chemotherapy added to their treatment. All patients from groups A and B completed up to 18 cycles of treatment with trastuzumab and pertuzumab. By the end of the trial, roughly 30% of those randomly assigned to group B received chemotherapy-free treatment.
A simplified schematic representation of the study design is shown below.
Promising Implications for HER2 Breast Cancer Treatment
Dr. Javier Cortés emphasizes the significance of this study, highlighting the potential for a future therapeutic option that reduces toxicity and improves the quality of life for patients without compromising treatment efficacy. “The most remarkable finding is that after 3 years of follow-up after surgery, we observed that only 12 patients had experienced a recurrence of the oncological disease, which means that 95.4% of patients remain cured with this follow-up time,” explains Dr. Cortés.
“In addition, 99% of patients who received anti-HER2 therapy without chemotherapy did not experience a recurrence of the disease after three years of follow-up.” Dr. José Pérez elaborates, "The results of the second primary objective of this study bring us closer and closer to the end of chemotherapy in a significant percentage of patients with this type of tumors.”
Dr. Antonio Llombart-Cussac also outlined the importance of designing more efficient strategy-based clinical trials with adaptive designs, as they expedite the delivery of effective therapies to patients. “It is critical to design more efficient strategy-based clinical trials with adaptive designs to bring effective therapies to patients in the shortest amount of time,” explains Dr. Llombart-Cussac.
Understanding the Impact of PHERGain on Breast Cancer Treatment
These results are a significant step toward minimizing the use of chemotherapy in a considerable percentage of patients with HER2-positive early breast cancer. With the advent of advanced anti-HER2 therapies and their high anti-tumor efficacy, the prognosis for these tumors has greatly improved. The scientific community's current focus is on developing treatment strategies that can cure patients without resorting to chemotherapy, known for its toxic side effects. The PHERGain trial addresses this critical challenge, aiming to eliminate unnecessary and harmful treatments while maintaining positive patient outcomes.
MEDSIR's dedication to advancing clinical research in oncology has proven instrumental in bringing effective therapies to patients, and their ongoing efforts continue to shape the future of breast cancer treatment.