Editor's Note: With continuous advancements in medical research, treatment strategies for triple-negative breast cancer (TNBC) are also evolving. From June 14-16, 2024, the 5th Comprehensive Cancer Treatment Academic Conference of the Xinghai Medical Forum was held in the romantic city of Dalian. Multiple significant studies on TNBC treatment were highlighted at ASCO, including the application of platinum-based therapies, new adjuvant treatment models, intensified adjuvant treatments, and the use of immunotherapy and ADCs in (neo)adjuvant settings. Oncology Frontier invited Professor Sifeng Tao from The Second Affiliated Hospital Zhejiang University School of Medicine and Professor Hui Liu from Sun Yat-sen University Cancer Center to discuss these latest research advancements in depth.Oncology Frontier: Regarding intensified adjuvant treatment (including initial high-risk and non-pCR after neoadjuvant therapy), the A-BRAVE study on immunotherapy was reported at this year’s ASCO conference. What do you think about the study results, and how would you consider individualized intensified adjuvant treatment for TNBC patients?
Professor Sifeng Tao: The A-BRAVE study presented at the ASCO conference focused on TNBC patients receiving a one-year intensified treatment with an immune checkpoint inhibitor, specifically avelumab, after completing adjuvant (including neoadjuvant or adjuvant) therapy. This study revealed the potential of immune checkpoint inhibitors in TNBC treatment. For example, avelumab has shown some benefits in disease-free survival (DFS) in neoadjuvant and adjuvant settings. However, results from various other immune checkpoint inhibitor studies have been mixed, with both positive and negative outcomes, making us cautious about their efficacy in early TNBC treatment. Each study’s results need to be carefully evaluated.
The A-BRAVE study’s current results indicate that an additional year of avelumab treatment after completing adjuvant therapy in high-risk TNBC patients did not significantly improve DFS, with a numerical difference of 5.1% but without statistical significance. However, in the secondary endpoint, the treatment showed a 34% benefit in overall survival (OS), offering a glimmer of hope. The study will continue to explore the relationship between PD-L1 expression levels and treatment efficacy, but this data is not yet available.
As further research progresses and follow-up periods extend, we hope the A-BRAVE study will provide more insights into the effectiveness of immune checkpoint inhibitors in TNBC treatment. At this stage, due to the preliminary results not showing significant DFS benefits, we remain cautious in clinical practice about using immune checkpoint inhibitors as intensified adjuvant treatment post-adjuvant therapy. We will continue to individualize adjuvant treatment for TNBC based on existing evidence, such as considering capecitabine intensification or other targeted immune therapies for specific mutations.
Nonetheless, the A-BRAVE study provides direction and shows the potential and hope for immune checkpoint inhibitors in TNBC treatment. We look forward to more in-depth studies in the future revealing their efficacy and mechanisms, offering more treatment options and hope to TNBC patients.
Oncology Frontier: Immunotherapy and ADCs have been extensively explored in advanced TNBC, accumulating considerable experience in managing toxic side effects. If immunotherapy and ADCs are applied in the (neo)adjuvant setting, how should safety management be conducted to ensure patients smoothly navigate the perioperative period?
Professor Hui Liu: The objectives of neoadjuvant therapy for early breast cancer and salvage therapy for advanced breast cancer differ significantly. The primary goal of neoadjuvant therapy is to achieve a cure, which means we must avoid severe adverse events from neoadjuvant therapy that could deprive patients of the opportunity for surgical treatment or even endanger their lives. Following the results of the Keynote-522 study, pembrolizumab has been approved for neoadjuvant treatment of early TNBC, increasing its clinical application frequency.
Compared to chemotherapy, immune-related adverse events (irAEs) from immunotherapy have a lower overall incidence, and patients generally tolerate them better. However, immunotherapy has unique characteristics, involving multiple organs, being insidious, having limited direct evidence, and high mortality rates from severe irAEs. Thus, clinicians must be well-versed in managing irAEs when using neoadjuvant immunotherapy. In clinical practice, close monitoring and careful assessment are necessary for early detection and treatment. Domestic expert consensus and CSCO guidelines provide recommendations for managing irAEs.
Overall, our management strategy should focus on prevention. Before treatment begins, we must thoroughly evaluate the patient’s condition to determine suitability for immunotherapy. If irAEs occur, they should be accurately graded and appropriately treated. Our goal is comprehensive management to ensure patients receive the best therapeutic effect from neoadjuvant immunotherapy while minimizing adverse event risks.
