Neoadjuvant Chemotherapy with Trastuzumab with or without Concurrent Radiotherapy in HER2-Positive Locally Advanced Inoperable Breast Cancer- A Phase 2 Randomized Controlled Trial (NEOTRAC STUDY).

Abstract

The role of neoadjuvant concurrent chemoradiation therapy (NACCRT) with anti-HER2 therapy in locally advanced breast cancer (LABC) remains unexplored. We conducted a phase II randomized trial to evaluate whether NACCRT combined with trastuzumab improves pathological complete response (pCR) compared with standard neoadjuvant chemotherapy (NACT) in patients with HER2-positive inoperable LABC. Patients with newly diagnosed, inoperable HER2-positive LABC were randomized 1:1 to receive NACT with trastuzumab (Arm A) or NACCRT with trastuzumab (Arm B). Both arms received anthracycline- and taxane-based chemotherapy with trastuzumab. Arm B received concurrent radiotherapy (RT) (46 Gy to the breast and regional nodes) during paclitaxel and trastuzumab, followed by mastectomy, whereas Arm A received sequential RT (50 Gy). The primary endpoint was pCR; secondary endpoints included survival, operability, toxicity, and treatment duration. A total of 118 patients were evaluated (Arm A, n=62; Arm B, n=56). Median age was 50 years, and all patients had stage III disease. pCR rates were 46.6% in Arm A and 50.9% in Arm B (P=0.64), with no differences by subgroups (hormone receptor status, menopausal status, tumor size, and stage grouping). The median follow-up was 36 months. Three-year EFS was 79.8% in Arm A and 76.8% in Arm B (P = 0.89), while OS was 88.7% in Arm A and 87.4% in Arm B (P = 0.63). Median treatment duration was significantly shorter with NACCRT (193.1 vs 262.9 days; p < 0.0001). Surgical wound morbidity occurred in 6.9% (4/58) of Arm A versus 16.4% (9/55) of Arm B (P = 0.15). Grade 3 radiation dermatitis of 5.5% (3/55) and neutropenia 3.6% (2/55) were observed only in Arm B. No cardiac toxicity was observed. NACCRT with trastuzumab is feasible and safe, significantly shortens overall treatment duration, and does not compromise survival. This strategy warrants further evaluation in selected patients where treatment efficiency is a priority.