Real-world response rates in patients with human epidermal growth factor receptor 2-positive breast cancer after neoadjuvant treatment using dual human epidermal growth factor receptor 2 blockade.

INTRODUCTION: Breast cancer (BC) is the most commonly diagnosed malignancy among women globally and in India. The human epidermal growth factor receptor 2 (HER2)-positive subtype is associated with aggressive disease and poorer prognosis; however, neoadjuvant therapy combining dual HER2 blockade with chemotherapy has been shown to improve pathological complete response (pCR) rates. This study evaluated the real-world effectiveness of dual HER2 blockade in the Indian setting. METHODS: This ambispective, descriptive real-world study was conducted at KIMSHEALTH, Trivandrum, Kerala (1 October 2019-30 April 2025), comprising retrospective (1 October 2019-30 April 2024) and prospective (1 May 2024-30 April 2025) phases. Patients with HER2-positive early BC receiving intravenous (IV) or subcutaneous (SC) pertuzumab and trastuzumab were included. The primary endpoint was pCR. Secondary endpoints included comparison of pCR between the IV and SC groups; assessment of chemotherapy regimen, disease stage, and hormonal status on outcomes; and evaluation of treatment-related toxicities. RESULTS: A total of 74 patients (35: retrospective; 39: prospective) (mean age: 56.8 ± 9.1 years) were included in the study; 52 (70.3%) received SC, and 22 (29.7%) received IV dual HER2 blockade. The overall pCR rate was 51.4% (SC: 44.2%; IV: 68.2%; p=0.06). Tumor stage (p=0.044) and composite clinical stage (tumor, node, and metastasis) (p=0.019) were significantly associated with pCR in the overall population, whereas estrogen receptor (ER) status was not associated with pCR (p=0.064). Multivariate analysis identified the composite clinical stage as an independent predictor of pCR (odds ratio: 0.242; p=0.012). Anemia was the most common toxicity, followed by hepatic toxicity, with comparable safety between the SC and IV groups. DISCUSSION: Neoadjuvant dual HER2 blockade in HER2-positive BC is effective and well tolerated in the Indian real-world setting, with tumor stage and composite clinical stage significantly influencing response, while ER status showed no significant association with pCR. SC and IV dual HER2 blockade demonstrated comparable efficacy and safety outcomes. These findings, which are consistent with historical data, further reinforce the therapeutic advancement from trastuzumab-based therapy to dual HER2 blockade, highlighting its improved effectiveness and clinical importance in the neoadjuvant treatment of HER2-positive BC.