Editor's Note: From August 2-4, 2024, the Seventh Tumor Precision Diagnosis and Treatment Conference and the Tenth Breast Cancer Individualized Treatment Conference (COMB), hosted by the China Cancer Foundation and the Beijing Breast Disease Prevention and Treatment Society, were grandly held in Beijing. The conference brought together the latest advancements in individualized precision treatment of breast cancer in China, providing a broad stage for promoting new concepts, developing new technologies, and creating new models in the breast cancer field. "Oncology Frontier" specially interviewed the chairman of the COMB conference, Academician Binghe Xu from the Cancer Hospital , Chinese Academy of Medical Sciences and Peking Union Medical College, to highlight the key points of COMB, outline the blueprint for the development of innovative breast cancer drugs in China, and guide the research directions for immunotherapy in breast cancer.

Oncology Frontier: As the chairman of the COMB conference, can you introduce the highlights of this conference?

Academician Binghe Xu: This conference has many highlights. First, as always, it focused on the precision treatment and individualized treatment of breast cancer. It is well-known that individualized treatment and precision treatment are among the most important development trends in breast cancer research. This conference reviewed the current status and future development trends of precision diagnosis and treatment of breast cancer from basic research, translational medicine to clinical trials.

Second, the status of Chinese clinical research is increasing, and its influence on the world is gradually strengthening. This conference emphasized the latest advancements in breast cancer treatment in China, including new drug development, clinical trials of new drugs, and new guidelines impacting breast cancer diagnosis and treatment.

Third, adhering to the tradition of precision treatment, this conference reviewed the latest research progress and future development trends by molecular subtyping of breast cancer. In the field of hormone receptor-positive (HR+) breast cancer, we focused on endocrine therapy combined with CDK4/6 inhibitors, PAM pathway-related inhibitors, and antibody-drug conjugates (ADC) for HER2-low expression. In the field of triple-negative breast cancer (TNBC), we explored new solutions and ideas such as TNBC reclassification, targeting, and immunotherapy. In the field of HER2-positive breast cancer, we reviewed and anticipated the progress of macromolecular monoclonal antibodies, small molecule targeted drugs, and ADCs.

Lastly, in the area of new drug development, China’s anti-tumor drug development started in the 1960s and has made significant progress in recent years, particularly in the past decade. At the 2024 American Society of Clinical Oncology (ASCO) annual meeting, China presented more than 30 oral reports, many related to new drug development, highlighting the strong development of new drugs in China. It should be noted that there is still a gap between China and the world’s advanced level in new drug development. Therefore, we must remain humble and continue to strengthen basic and translational research in oncology, clinical research, policy support, and capital investment to enhance enterprise innovation, improve researchers’ development levels and capabilities, and continuously develop new targets and innovative drugs to catch up with and narrow the gap with the international forefront. I believe that with joint efforts, China’s anti-tumor innovative drug development will continue to progress, and the day it reaches the world’s forefront will come soon.

Oncology Frontier: During the conference, you shared a wonderful report on “China’s Anti-Tumor New Drug Development.” In your opinion, what challenges does China’s current anti-tumor new drug development face, and what are the future directions for efforts?

Academician Binghe Xu: China’s anti-tumor new drug development faces several challenges. First, our innovation ability and originality need improvement. Although there has been significant progress, most new drug development is in the follow-up stage, with few original drugs and a lack of globally influential drugs.

Second, we need to continue improving the quality and efficiency of clinical trials. Many clinical research institutions in China have aligned with international advanced levels, but there is still room for improvement in clinical trial system construction, quality control, ethical review, and patient recruitment efficiency, which are crucial factors affecting the speed and success rate of new drug development.

Third, funding and risk-sharing require multi-party cooperation. It is well-known that new drug development is a long process, often taking around ten years, with a high failure rate. Therefore, we need to establish diversified financing channels, including national, venture capital, and enterprise self-financing, to ensure the continuous development of innovative drugs, benefiting more cancer patients.

Fourth, talent cultivation is crucial. Although China invests heavily in basic research, it lacks leading talents, especially those with global influence. Many cancer treatment targets are discovered through basic research abroad, leading to quicker and earlier development of targeted innovative drugs. China publishes many articles and obtains numerous patents in basic research annually, but translating these research results into clinical applications still requires improvement.

Fifth, clinical research capabilities need enhancement. We need to train more clinical scientists to improve clinical trial standards, assisting China in conducting more clinical trials. Currently, there is a lack of talents who can lead nationwide or even global multi-center clinical research and influential clinical trial experts. Therefore, we must train more young and middle-aged talents to continuously improve our clinical trial capabilities.

I believe that with joint efforts from basic research, translational medicine, and clinical trials, supported by pharmaceutical companies and the capital market, we can improve China’s anti-tumor drug development capabilities.

Oncology Frontier: Immunotherapy is increasingly valued in breast cancer clinical research at home and abroad. What is the application prospect of immunotherapy in breast cancer, known as a “cold tumor”?

Academician Binghe Xu: Immunotherapy has achieved excellent therapeutic effects in many tumors, such as lung cancer and lymphoma, but its application in breast cancer has been less effective, often considered a “cold tumor” for immunotherapy. Currently, international drug regulatory authorities have only approved immunotherapy combined with chemotherapy for first-line treatment of TNBC, but the optimal combination still requires further research. My center explored different chemotherapy regimens combined with immunotherapy, eventually finding that metronomic chemotherapy with vinorelbine combined with immunotherapy was superior to conventional treatment. These results were recently published in “Nature Medicine,” garnering international attention and opening new avenues for immunotherapy.

Additionally, we are exploring predictive methods for immunotherapy efficacy. For example, in combining immunotherapy with anti-angiogenic drugs, we found some biomarkers that could predict immunotherapy efficacy through dynamic ctDNA monitoring. This is another advancement beyond traditional PD-L1 positivity predicting efficacy. Moreover, the application of immunotherapy in advanced breast cancer and more combination regimens are worth exploring.

In HR+ breast cancer, initial results from neoadjuvant immunotherapy combined regimens have shown an improvement in pathological complete response (pCR) rates, although overall survival (OS) data is not yet available, requiring further observation. In HER2-positive breast cancer, while anti-HER2 targeted drugs have achieved good efficacy, some patients still experience recurrence and metastasis. Whether combining targeted and immunotherapy is effective for these patients is under investigation in a nationwide, multi-center clinical study. Preliminary results show that large molecule monoclonal antibodies combined with immunotherapy achieved good efficacy in the first-line treatment of advanced breast cancer, with a high response rate and longer PFS compared to conventional treatment, effective regardless of PD-L1 status. Based on this, further exploration is needed to determine the optimal combinations and application timing of immunotherapy in HER2-positive breast cancer.

In summary, besides achieving good results in TNBC, there is significant exploration space for the application of immunotherapy in HR+ and HER2-positive breast cancer. We hope these explorations will broaden the application prospects of immunotherapy. I also look forward to this day coming soon.