PHERGain: Excellent Outcome Without Chemotherapy for Patients with Early Breast Cancer

De-escalating therapy when it is unneeded, which avoids the associated toxicity, is a goal of clinical research, particularly as new tools can discriminate early between patients who are benefiting and those who are not. The industry-sponsored PHERGain trial is one recent example of using early signals provided by ¹⁸fluorine-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG-PET) to determine the course of therapy.

In this European, multicenter, open-label, phase 2 trial, patients with HER2-positive invasive breast cancer (stages I–IIIa) were randomized in a 1:4 ratio to: (A) standard docetaxel, carboplatin, trastuzumab, and pertuzumab (TCHP) or (B) trastuzumab and pertuzumab (71 and 285 patients, respectively). Patients underwent surgery, received endocrine therapy if appropriate, and received HER2-directed therapy postoperatively. They received ¹⁸F-FDG-PET scans at baseline and after 2 cycles of neoadjuvant therapy. Patients in group B who showed response on ¹⁸F-FDG-PET continued initial therapy without chemotherapy; for nonresponders, therapy was switched to 6 cycles of TCHP.

After 8 treatment cycles, as previously reported, 38% of group B responders achieved pathologic complete response (pCR; Lancet Oncol 2021; 22:858). Now, researchers have reported invasive disease-free survival (iDFS) at 3 years after surgery, the other coprimary endpoint. At a median follow-up of 43 months, the iDFS was 94.8% in group B patients who underwent surgery (n=267), meeting the statistical requirement for significance (iDFS in group A, 98.3%). No new safety signals were seen.