Editor's Note: HER2-positive breast cancer accounts for about 20% of all breast cancer cases. Since the advent of anti-HER2 therapies such as trastuzumab, the survival of HER2-positive breast cancer patients has significantly improved. The introduction of small molecule TKIs has further expanded treatment options. To explore the real-world treatment patterns, clinical application, efficacy, and safety data of neratinib in Chinese patients with early HER2-positive breast cancer, Professor Jin Zhang from Tianjin Medical University Cancer Institute and Hospital, along with multiple hospitals, conducted the NER-Tree study. The study's results were presented in a poster session at the 2024 ESMO BC conference. “Oncology Frontier” invited Professor Jin Zhang to discuss the study.Oncology Frontier: Can you explain how treatment patterns for HER2-positive breast cancer patients have evolved with the increasing availability of neoadjuvant and adjuvant anti-HER2 therapies?
Professor Jin Zhang: HER2-positive breast cancer accounts for about 20% of all breast cancer cases. Currently, there are standard treatment recommendations for neoadjuvant, adjuvant, and advanced stage treatments. In clinical practice, for HER2-positive breast cancer patients suitable for neoadjuvant therapy, we first recommend standard neoadjuvant treatment followed by local therapy. If the pathology shows non-complete remission after local therapy, the patient should continue with adjuvant chemotherapy combined with anti-HER2 therapy. If the patient progresses to an advanced stage, they should continue to receive anti-HER2-based combination therapy in first-line, second-line, and later-line settings. Under standardized protocols, the disease-free survival and overall survival of HER2-positive breast cancer patients have significantly improved.
Oncology Frontier: At the ESMO BC conference, the NER-Tree study, which you led, was selected for a poster presentation. Can you introduce the latest progress of this study and its implications for the treatment of early HER2-positive breast cancer patients in China?
Professor Jin Zhang: The NER-Tree study was selected for a poster presentation at the 2024 ESMO conference. This multicenter, open-label, single-arm, non-interventional study evaluated the effectiveness of extended adjuvant therapy with neratinib in early breast cancer patients. The study included 500 HER2-positive early breast cancer patients from 30 centers in China who had completed adjuvant trastuzumab therapy and planned to receive 1 year of extended adjuvant therapy with neratinib. Patients will undergo 12 months of neratinib therapy followed by 12 months of follow-up. The primary and secondary objectives were to describe real-world adjuvant therapy patterns and observe the safety of neratinib treatment.
As of September 21, 2023, 250 patients were included in the analysis. The median age of patients was 50.0 years, with 161 (64.4%) being postmenopausal. At initial diagnosis, 57.2% of breast cancer patients were HR+/HER2+; 24.4% were cT1, and 57.2% were cT2. Additionally, 73.6% were N+, and 88.4% were stage II-III HER2-positive breast cancer. Eighty-four patients (33.6%) received neoadjuvant therapy, with 46 not achieving pCR. Regardless of achieving pCR, the most common neoadjuvant regimen was trastuzumab combined with pertuzumab. All 250 patients (100%) received adjuvant therapy, with 220 (88%) receiving trastuzumab combined with pertuzumab, and 26 (10.4%) receiving trastuzumab alone.
The study provides larger sample size data on the efficacy and safety of neratinib as extended adjuvant therapy in early breast cancer patients. The study also suggests that using small molecule TKIs for anti-HER2 intensification in the second year following the first year of adjuvant anti-HER2 therapy can further prolong disease-free survival in HER2-positive breast cancer patients.
Oncology Frontier: How is the quality of life for patients undergoing neratinib treatment? Based on your experience, what are the key considerations during treatment with this drug?
Professor Jin Zhang: During breast cancer treatment, we need to manage patients throughout the entire treatment cycle. Adverse reactions to small molecule TKIs, such as diarrhea, commonly occur in the digestive tract. Considering the mechanism of action and safety of neratinib, we should first assess the drug dosage and the patient’s tolerance. At a tolerable dosage, if patients experience gastrointestinal adverse reactions like diarrhea, they should promptly receive antidiarrheal treatment. Additionally, adjusting the dose of neratinib is necessary to ensure patients complete one year of adjuvant therapy.
Oncology Frontier: What are the key considerations in clinical treatment for HER2-positive breast cancer? Please share your insights based on your clinical experience.
Professor Jin Zhang: HER2-positive breast cancer currently has the best treatment outcomes among all breast cancer subtypes. Anti-HER2 therapies have significantly improved the survival of HER2-positive breast cancer patients, but tumor heterogeneity is a challenge we face in each patient’s treatment. Therefore, before starting clinical treatment, we should clearly define the patient’s TNM stage. For patients suitable for neoadjuvant therapy, clinicians should promptly recommend neoadjuvant therapy, as anti-HER2 combined chemotherapy can significantly improve pCR rates, offering opportunities for breast and axillary conservation.
Subsequently, we can provide follow-up adjuvant intensified anti-HER2 therapy based on different patients’ pathological complete response status. This not only benefits disease-free survival but also prolongs overall survival. Therefore, for HER2-positive breast cancer patients, precise diagnosis and treatment throughout the entire process and lifecycle are essential to extending survival and are particularly crucial for some early-stage HER2-positive breast cancer patients.
