Editor's Note: The 47th San Antonio Breast Cancer Symposium (SABCS) successfully took place in San Antonio, USA. As one of the largest and most prestigious scientific gatherings in breast cancer research, SABCS showcased the latest findings, clinical practices, treatment advances, and technological innovations over the past year. Among the presented studies, an oral presentation (GS3-05) analyzed the efficacy of neoadjuvant chemotherapy combined with atezolizumab, followed by adjuvant atezolizumab in triple-negative breast cancer (TNBC) patients. Oncology Frontier invited Dr. Ting Luo from the West China Hospital of Sichuan University to introduce this study and provide expert commentary.

Study Title

• NSABP B-59/GBG-96-GeparDouze: A Randomized Double-Blind Phase III Clinical Trial of Neoadjuvant Chemotherapy with Atezolizumab or Placebo Followed by Adjuvant Atezolizumab or Placebo in Patients with Stage II and III Triple-Negative Breast Cancer

Dr. Ting Luo：Due to the high heterogeneity of TNBC and the lack of effective targets, chemotherapy remains the primary systemic treatment. In recent years, immunotherapy has become a research hotspot in TNBC treatment, showing promising results, especially in the neoadjuvant setting. Clinical trials involving PD-1 inhibitors like pembrolizumab and PD-L1 inhibitors like atezolizumab have been actively conducted.

The previously reported IMpassion031 study showed that adding atezolizumab to standard chemotherapy significantly improved the pathological complete response (pCR) rate in early TNBC patients receiving neoadjuvant therapy. However, this improvement did not statistically translate into enhanced event-free survival (EFS), disease-free survival (DFS), or overall survival (OS), although numerical gains were observed compared to the control group.

Similarly, this study also demonstrated that atezolizumab improved pCR rates in TNBC patients, but this did not result in overall EFS benefit for the entire study population. However, noteworthy improvements in EFS were observed in subgroups with a high tumor burden (lymph node-positive, tumors >3 cm) or high immune activation (tumor-infiltrating lymphocytes, TILs ≥30%), aligning with the mechanism of action of immunotherapy. This finding provides supporting evidence for identifying and focusing on specific patient populations that could benefit from immunotherapy.

Another relevant study, KEYNOTE-522, explored the efficacy of neoadjuvant chemotherapy combined with pembrolizumab in early-stage TNBC. The study confirmed that chemotherapy combined with pembrolizumab improved both pCR and EFS compared to chemotherapy alone. Although a direct head-to-head comparison isn’t possible, EFS rates for patients treated with atezolizumab and pembrolizumab were comparable at 85.2% and 84.5%, respectively. However, differences were noted in the outcomes of their respective control groups, with EFS rates of 81.9% for atezolizumab and 76.8% for pembrolizumab.

This difference may not only relate to the intrinsic efficacy of the immune checkpoint inhibitors but also to variations in chemotherapy regimens and trial designs. For instance, in the NSABP B-59/GBG-96 GeparDouze study, 996 out of 1,550 patients (64.25%) received a dose-dense AC/EC neoadjuvant chemotherapy regimen, potentially contributing to the improved EFS in the control group. Additionally, patients who did not achieve pCR were allowed to receive standard intensified treatments (e.g., capecitabine, olaparib) post-neoadjuvant therapy, unlike in KEYNOTE-522, which did not incorporate similar follow-up treatments. This could have further improved overall survival in the NSABP B-59/GBG-96 GeparDouze cohort, diminishing the relative benefit observed with atezolizumab.

However, these findings are based on historical comparisons. Exploratory analyses like these cannot provide definitive guidance for clinical practice. More robust research data is required to conclusively determine the efficacy of immunotherapies like atezolizumab in TNBC treatment.

Dr. Ting Luo

• Deputy Director, Breast Disease Center, West China Hospital, Sichuan University
• Chief Physician, Doctor of Medicine, Master’s Supervisor
• Council Member, Chinese Society of Clinical Oncology (CSCO)
• Standing Member, CSCO Youth Expert Committee
• Member, CSCO Breast Cancer Expert Committee (CSCO BC)
• Member, Breast Cancer Committee, Chinese Anti-Cancer Association (CBCS)
• Secretary-General, Breast Cancer Integrated Prevention and Screening Committee, Chinese Anti-Cancer Association
• Vice Chair, Yangtze River Breast Cancer Study Group (YBCSG)
• Chair, Breast Cancer Committee, Sichuan International Medical Exchange & Promotion Association
• Vice Chair, Breast Cancer Committee, Sichuan Anti-Cancer Association
• Vice President, Breast Professional Branch, Sichuan Medical Association
• Standing Member and Youth Chair, Breast Disease Prevention and Control Branch, Sichuan Preventive Medicine Association
• Vice Chair, Breast Cancer Committee, Sichuan Oncology Society
• Recipient of the “Outstanding Contribution Award in Breast Cancer” from the Third “People’s Good Doctor · Jinshan Camellia Project”