Editor’s Note: The "Northern Breast Cancer Salon Annual Progress Review" was held from January 3–5, 2025, in Beijing. The conference comprehensively reviewed the latest advances in breast cancer diagnosis, treatment, and research over the past year, delving into the latest findings for various breast cancer subtypes and their impact on clinical practice. The conference also focused on discussions regarding updates to the CSCO BC guidelines, providing scientific guidance for clinical practice in breast cancer. At the event, Oncology Frontier invited Dr. Kun Wang from Guangdong Provincial People's Hospital to review the past year’s advancements in the field of early triple-negative breast cancer (TNBC) treatment.

Oncology Frontier: Could you briefly review the key advances in the field of early triple-negative breast cancer over the past year?

Dr. Kun Wang: As we know, triple-negative breast cancer is the subtype with the poorest prognosis among breast cancers. Compared to Luminal and HER2-positive breast cancers, TNBC is associated with earlier recurrence and worse outcomes. However, continuous exploration of treatment strategies has significantly improved outcomes for TNBC patients. The evolution of neoadjuvant treatment for early TNBC has progressed from anthracycline regimens to anthracycline + taxane regimens, and further to taxane + platinum and taxane + platinum + immunotherapy regimens, with pathologic complete response (pCR) rates steadily improving. The KEYNOTE-522 study demonstrated that pembrolizumab not only significantly increased the pCR rate but also achieved a 5-year overall survival (OS) rate of 86.6%, significantly better than the placebo group’s 81.7% (HR=0.66, 95% CI: 0.50–0.87, P=0.0015). This suggests that TNBC patient survival outcomes are approaching those of Luminal and HER2-positive breast cancer patients.

Several milestones have been achieved in the field of TNBC treatment:

  1. The Role of Platinum Agents: The PEARLY clinical study, published last year, evaluated the efficacy of carboplatin in combination with anthracycline and taxane-based regimens for early-stage (I–III) TNBC in both neoadjuvant and adjuvant settings. Results showed that patients receiving carboplatin-based chemotherapy had significantly better event-free survival (EFS) compared to those receiving standard chemotherapy alone. The 5-year EFS rate in the carboplatin group was 81.9%, 7.5% higher than the control group’s 74.4%. This study reaffirmed the value of platinum agents in early TNBC treatment. Earlier studies had shown that platinum agents improved pCR rates in neoadjuvant therapy, and now there is evidence that they also enhance EFS in systemic treatment, cementing their importance in early TNBC.
  2. Immunotherapy: The KEYNOTE-522 study demonstrated that the addition of pembrolizumab increased the pCR rate by 13.6% (64.8% vs. 51.2%), improved 5-year EFS by 9% (81.3% vs. 72.3%), and raised 5-year OS by about 5% (86.6% vs. 81.7%) compared to the placebo group. These improvements in pCR, EFS, and OS firmly established the role of immunotherapy in early TNBC treatment.

At the 2024 SABCS conference, the NSABP B-59/GBG-96-GeparDouze study evaluated the efficacy of adding atezolizumab to a neoadjuvant taxane + carboplatin regimen and adjuvant atezolizumab in early TNBC patients. The study included 1,550 patients who were randomized 1:1 to the atezolizumab or placebo groups. Although this study was similar in design to KEYNOTE-522, it used a different immunotherapy agent. The 4-year EFS rates were 81.9% and 85.2% for the atezolizumab and placebo groups, respectively, with no statistically significant difference (HR 0.8; 95% CI: 0.62–1.03; P=0.08).

Based on findings from atezolizumab in advanced stages (IMpassion 130, IMpassion 131) and neoadjuvant stages (IMpassion 031), as well as durvalumab in GeparNuevo, it appears that positive results in early TNBC immunotherapy are primarily seen with PD-1 inhibitors.

Additionally, at the 2024 SABCS conference, Professor Shao Zhimin from Fudan University Cancer Hospital presented findings from the CamRelief study (Abstract GS3-06), a prospective randomized controlled trial assessing the efficacy and safety of camrelizumab combined with chemotherapy in early or locally advanced TNBC. This study, designed to reflect the realities of clinical practice in China, included patients with high-risk disease: 35.8% had stage III disease at baseline, 70.5% had lymph node involvement (9.1% N3), and patients were treated with dose-dense chemotherapy regimens.

Results showed that the pCR rate in the camrelizumab + chemotherapy group was 56.8% (95% CI: 50.0–63.4), compared to 44.7% (95% CI: 38.0–51.6) in the placebo + chemotherapy group (difference: 12.2%; 95% CI: 3.3–21.2; one-sided P=0.0038). pCR benefits were observed regardless of PD-L1 expression, lymph node status, or baseline disease stage. These results, simultaneously published in JAMA, established camrelizumab + chemotherapy as a promising option for early high-risk TNBC.

Oncology Frontier: Reflecting on the past year, the KEYNOTE-522 study has been a major breakthrough in early TNBC. However, it also raises questions. How do you view the insights and challenges this study brings to early TNBC treatment?

Dr. Kun Wang: The KEYNOTE-522 study demonstrated improvements not only in short-term outcomes such as pCR but also in long-term outcomes like EFS and OS. It perfectly established the role of neoadjuvant chemotherapy combined with immunotherapy in early TNBC treatment, marking a milestone in the field.

Oncology Frontier: The I-SPY 2.2 study presented compelling results at the 2024 ASCO and ESMO conferences, particularly regarding the efficacy of Dato-DXd monotherapy and its combination with durvalumab in specific subtypes. How do you evaluate these findings and their impact on early TNBC treatment?

Dr. Kun Wang: The I-SPY 2.2 study introduced several innovations in design:

  1. Innovative Design: The study evolved through I-SPY 1.0, 2.0, and 2.2 phases, featuring three treatment blocks (A, B, and C). Block A used Dato-DXd + durvalumab, with more than half of the patients achieving pCR. This suggests that many patients could achieve pCR without requiring chemotherapy and immunotherapy.
  2. New Approach: The study designed three blocks for neoadjuvant treatment, allowing some patients to achieve pCR after just 4 or 8 cycles of treatment. This enables more precise prediction of which patients are likely to achieve pCR, potentially reducing the need for chemotherapy cycles—a distinctive feature of this clinical research.

Dr. Kun Wang

Deputy Director of Guangdong Provincial People’s Hospital Cancer Center Professor and Doctoral Supervisor Board Member of CSCO, Standing Committee Member of the Breast Cancer Committee Standing Committee Member of the Breast Cancer Professional Committee, Chinese Anti-Cancer Association Recipient of the 2019 National Distinguished Physician Award NeoCART Study Included in the 2021 NCCN Breast Cancer Guidelines Recipient of the 2023 “Outstanding Contribution Award” in the Breast Cancer Field by People’s Good Doctors

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Last updated on 2025.01.24