Clinical Summary:

• Design/Population: In the phase 2 PHERGain-2 trial, patients with HER2-positive, node-negative early breast cancer received neoadjuvant pertuzumab plus trastuzumab followed by response-adapted adjuvant therapy based on pCR. 
• Key Outcomes:  Neoadjuvant trastuzumab/pertuzumab achieved high pathologic complete response rates with preservation of health-related quality of life and manageable toxicity.
• Clinical Relevance: These findings support pCR guided chemotherapy omission in select patients with early HER2-positive breast cancer.

Results from the phase 2 PHERGain-2 trial suggest that selected patients with HER2-positive early breast cancer may be able to forgo chemotherapy with a pathologic complete response (pCR)-guided HER2-targeted treatment strategy without compromising quality of life. 

These results were presented by Antonio Llombart Cussac, MD, PhD, Hospital Arnau de Vilanova, Valencia, Spain, at the 2026 European Society for Medical Oncology (ESMO) Breast Cancer Congress in Berlin, Germany.

In this open-label, single-arm study, 396 previously untreated patients with centrally confirmed HER2-positive, node-negative early breast cancer received neoadjuvant pertuzumab plus trastuzumab once every 3 weeks for 8 cycles. Following surgical resection, adjuvant treatment was adapted based on pCR status. Patients who achieved pCR continued to receive pertuzumab plus trastuzumab to complete 18 cycles (n = 236). Patients with residual invasive or low-volume residual disease received trastuzumab emtansine for 10 cycles (n = 148). Patients with persistent nodal disease were permitted to receive an optional round of chemotherapy prior to trastuzumab emtansine (n = 7). Patients with hormone receptor-postive disease (n = 263) received endocrine therapy during both phases. 

The primary end point was health-related quality of life decline at 1 year post-neoadjuvant treatment.  Key secondary end points included 3-year recurrence-free survival (RFS) rate, pCR, and safety. 

At analysis, 98.7% of patients underwent surgical resection. A clinically meaningful decline in health-related quality of life occurred in 42.8% of patients overall, including 37.3% of patients who achieved pCR and 51.9% of patients with residual disease. A clinically meaningful decline in health-related quality of life occurred in 36.1% of patients who were hormone receptor-negative and 45.2% of patients who were hormone receptor-positive. 

Any-grade treatment-related adverse events were reported in 86.6% of patients and grade 3 treatment-related events were reported in 5.6% of patients. Serious adverse events were reported in 6.1% of patients. There was 1 treatment-related death which was due to trastuzumab emtansine-associated pneumonitis. 

“PHERGain-2 shows clinically meaningful [health-related quality of life] preservation, expected [pertuzumab plus trastuzumab and trastuzumab emtansine] toxicity, and an outstanding pCR rate comparable to standard regimens in this patient population,” concluded Dr Cussac. 

Source:

Cussac AL. Borrego MR, Perez Garcia JM, et al. Chemotherapy-free, pathological complete response (pCR)-guided strategy with trastuzumab-pertuzumab (HP) and T-DM1 in HER2+ early breast cancer (EBC): PHERGain-2. Presented at European Society for Medical Oncology (ESMO) Breast Cancer Congress; March 6 - 8, 2026; Berlin, Germany. 214O.