Dr McAndrew on the Implications of the PHERGain Study in HER2+ Breast Cancer

Nicholas P. McAndrew, MD, MSCE, health sciences clinical assistant professor, Hematology/Oncology, University of California, Los Angeles (UCLA), UCLA Health, discusses the implications of the phase 2 PHERGain study (NCT03161353) of chemotherapy de-escalation in patients with HER2-positive early breast cancer.

Actively leveraging neoadjuvant studies in breast cancer is necessary to both pinpoint patients requiring escalated therapy and identify those who could benefit from chemotherapy de-escalation, McAndrew begins, adding that it is essential to recognize the variability in breast cancers, particularly in patients with HER2-positive disease. Innovative studies like the PHERGain trial aim to address this challenge, he notes. Data from the trial were presented at the 2023 ASCO Annual Meeting. The study employed a pathologic complete response (pCR)–adapted strategy to determine the feasibility of utilizing a chemotherapy-free dual HER2-blockade regimen in patients with early HER2-positive breast cancer.

In the experimental arm, participants received the least toxic and most effective therapy- targeted therapy alone, McAndrew continues. This consisted of trastuzumab (Herceptin) and pertuzumab (Perjeta) with or without endocrine therapy. Generally, this targeted therapy is not as potent as chemotherapy for unselected patients. However, the study aimed to identify patients who did achieve a good response with the regimen.

Patients with a positive PET response or pCR after 2 treatment cycles, according to a PET scan,continued with the same treatment. Chemotherapy was added to the regimen for those who did not respond to targeted therapy alone, McAndrew expands.

The study demonstrated that approximately one-third of patients did not receive chemotherapy during the study and achieved comparable 3-year invasive disease-free survival rates to that of patients who underwent chemotherapy, he explains.

Although this PET-based, pCR-adapted strategy may not become the standard approach for all patients, it still an innovative trial design, he continues. Trials like PHERGain are crucial in moving away from a one-size-fits-all regimen. This personalized approach aims to maximize efficacy and minimize toxicity for individual patients, McAndrew concludes.