In the phase II PHERGain trial reported in The Lancet, Pérez-García et al found that a positron-emission tomography (PET)-based, pathologic complete response (pCR)-adapted treatment strategy produced “excellent” 3-year invasive disease–free survival results in patients with HER2-positive early breast cancer.
Study Details
In the open-label trial, 356 patients from sites in seven European countries were randomly assigned in a 1:4 ratio between June 2017 and April 2019 to receive either:
- Docetaxel at 75 mg/m2, carboplatin at AUC 6, trastuzumab at 600 mg, and pertuzumab at an 840-mg loading dose followed by 420-mg maintenance doses every 3 weeks (TCHP; group A, n = 71)
- A chemotherapy-free regimen of trastuzumab and pertuzumab with or without endocrine therapy every 3 weeks (group B, n = 285).
Fluorine-18–fluorodeoxyglucose (F-18–FDG) PET was performed at baseline and after two treatment cycles. Patients in group B were treated according to on-treatment PET results; those who were PET-responders continued with trastuzumab and pertuzumab with or without endocrine therapy for six cycles, and those who were PET-nonresponders were switched to receive six cycles of TCHP. After surgery, patients in group B who were PET-responders who did not achieve pCR received 6 cycles of TCHP, and all patients completed up to 18 cycles of trastuzumab and pertuzumab. The primary endpoints of the trial were pCR in group B PET-responders after two treatment cycles (results reported previously) and 3-year invasive disease–free survival in patients in group B who proceeded to surgery.
Key Findings
Surgery was performed in 63 patients (89%) in group A and 267 (94%) in group B. At the time of analysis (data cutoff in November 2022), median follow-up was 43.3 months (range = 0.0–63.0 months).
In group B, the estimated 3-year invasive disease–free survival rate was 94.8% (95% confidence interval [CI] = 91.4%–97.1%, P = .001), meeting the primary endpoint (excluding null hypothesis of ≤ 89%). Estimated 3-year disease-free survival was 94.8% (95% CI = 91.4%–97.1%) and estimated distant disease–free survival was 96.5% (95% CI = 94.3%–98.8%).
Among 86 PET-responders in group B who had pCR and thus did not receive study chemotherapy, estimated 3-year invasive disease–free survival was 96.4% (95% CI = 92.4%–100%). Among the 63 patients in group A who underwent surgery, estimated 3-year invasive disease–free survival, disease-free survival, and distant disease–free survival rates were 98.3% (95% CI = 95.1%–100%), 98.3% (95% CI = 95.1%–100%), and 98.3% (95% CI = 95.1%–100%), respectively.
Grade ≥ 3 treatment-related adverse events occurred in 62% of patients in group A and 33% of group B. Serious adverse events occurred in 28% vs 14% of patients. PET-responders in group B with pCR showed the lowest incidence of treatment-related grade ≥ 3 adverse events (1%) and had no serious adverse events.
The investigators concluded, “Among HER2-positive [patients with early breast cancer], a PET-based, pCR-adapted strategy was associated with an excellent 3-year invasive disease–free survival. This strategy identified about a third of patients who had HER2-positive early breast cancer who could safely omit chemotherapy.”
Antonio Llombart-Cussac, MD, of Hospital Arnau de Vilanova, Universidad Catolica de Valencia, Spain, is the corresponding author for The Lancet article.
Disclosure: The study was funded by F. Hoffmann-La Roche. For full disclosures of the study authors, visit thelancet.com.
