Editor’s Note: At the 2024 ESMO BC conference, Professor Qiang Liu from Sun Yat-sen Memorial Hospital, Sun Yat-sen University, presented a report titled “From Phase III Clinical Trials to Real-World Data: Bridging the Gap Between Clinical Trials and Clinical Practice.” This report delved into the treatment advances for HER2-positive breast cancer, the differences between clinical trials and real-world data, and how to better guide clinical practice. “Oncology Frontier” invited Professor Liu to share insights on his report and the disparities between clinical trials and clinical practice.
Oncology Frontier: You presented a report titled “Addressing Disparities Between Clinical Trials and Clinical Practice: From Phase III to Real-World Setting” at this year’s ESMO BC conference. Could you recap and share the key points?
Professor Qiang Liu: At the 2024 ESMO BC conference, Medscape organized a continuing medical education session focusing on clinical issues in HER2-positive breast cancer. This session was well-received, with a full house of attendees who expressed great appreciation for the insights shared by the experts. My presentation mainly discussed the differences between evidence from phase III clinical trials and real-world research data in treating HER2-positive breast cancer. How do we address these differences? How can we better guide clinical practice?
My report focused on several key aspects of HER2-positive breast cancer clinical trials. Designing clinical trials for HER2-positive breast cancer is particularly challenging because the standard treatment protocols (including neoadjuvant and adjuvant therapies) are continually evolving. Before trastuzumab was widely used in treating HER2-positive breast cancer, this subtype had the worst prognosis. Today, with advancements in anti-HER2 targeted therapies, HER2-positive breast cancer has become one of the breast cancer subtypes with the lowest risk of death. HER2 positivity is no longer a high-risk marker, which is significant for patients.
In 2013, at the St. Gallen conference, HER2 positivity was considered a high-risk marker for breast cancer. Today, HER2 positivity represents a marker for low-toxicity, highly effective targeted therapy, a change of particular importance to patients. My report and those of other professors also discussed the significant heterogeneity among HER2-positive breast cancer patients, such as differences between HR+/HER2+ and HR-/HER2+ breast cancers. These differences include varying pCR rates, the impact of pCR on prognosis, different choices in anti-HER2 targeted therapies, differences in patient age, recurrence cycles, and recurrence sites. We explored these issues in depth during the conference.
Overall, in current phase III clinical research, we rarely distinguish patients with early HER2-positive breast cancer based on HR status. However, real-world clinical research may supplement the treatment decision-making for early HER2-positive breast cancer. Mixing different patient types can reduce the specificity of drug treatment and the clinical significance of research conclusions. This limitation is a key focus of my report.
Oncology Frontier: In your view, what are the differences between phase III clinical trials and clinical practice, and how should clinicians navigate these differences to avoid disparate outcomes?
Professor Qiang Liu: In the medical field, the highest principle we follow for patient treatment is evidence-based medicine, primarily derived from the results of large phase III clinical trials. We cannot rely on the treatment effects of just one or a few patients but must validate findings through large-scale clinical trials involving hundreds or thousands of patients. If the results show that treatment A is significantly better than treatment B, then the study has persuasive power, unlike anecdotal evidence. This is the guiding value of phase III clinical trials for clinical practice.
However, phase III clinical trials also have limitations. For rare populations (e.g., male breast cancer, pregnancy-associated breast cancer), there are not enough cases to conduct phase III randomized controlled trials. Additionally, large phase III clinical trials often emphasize commonalities among patients while neglecting individual differences. Different patients may respond differently to drug treatments, and variations in dosage and side effects during treatment can also impact trial outcomes.
While the results of phase III clinical trials are the main basis for clinical diagnosis and treatment, real-world data provide a valuable supplement. We can refer to the results of phase III clinical trials for clinical operations, but in the absence of such data, we also need to explore real-world data to better guide clinical practice. Phase III clinical trials and real-world data complement each other, providing a more comprehensive reference for clinical practice.
Oncology Frontier: In clinical practice, should all patients follow the standards set by phase III clinical trials? Based on your clinical experience, could you share your insights on this matter?
Professor Qiang Liu: In clinical practice, treatment operations should first refer to the results of large-scale standardized phase III clinical trials. In most cases, at least 70% to 80% of patients can be treated according to these standards. However, with the rapid emergence of new targeted therapies for HER2-positive breast cancer and the quick evolution of treatment paradigms, phase III clinical trials may not cover all specific situations due to their long duration and large sample sizes.
When there are no clear phase III clinical trial guidelines, we need to supplement with real-world research data. Therefore, in clinical practice, if there are standard phase III clinical trial results available, we should follow these results for clinical operations and guidance. In the absence or inadequacy of such trials, we need to combine personal clinical experience and real-world data to provide the most optimized treatment plans for patients.
In summary, I believe “it’s better to have no books than to believe all books.” While we should be guided by the content of medical literature, blindly adhering to it without flexibility is not appropriate. The results of phase III clinical trials are crucial for changing clinical guidelines and advancing evidence-based medicine. However, combining real-world data with flexible application is necessary to provide the most optimized clinical treatment for patients.
Professor Qiang Liu
- Professor, Chief Physician, Researcher, Doctoral Supervisor
- Director of Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University
- Executive Vice President of Yixian Breast Cancer Hospital, Director of Breast Cancer Center, Director of Breast Surgery
- Member of the ESO-ESMO International Consensus Panel for Young Breast Cancer
- Executive Member and Deputy Secretary General of the Breast Cancer Professional Committee, Chinese Society of Clinical Oncology (CSCO)
- Executive Member of the Breast Cancer Professional Committee, China Anti-Cancer Association
- Executive Member of the Tumor Molecular Medicine Professional Committee, China Anti-Cancer Association
- Chair of the Breast Disease Branch, Guangdong Medical Association
- Chair-Elect of the Breast Cancer Professional Committee, Guangdong Anti-Cancer Association
- Deputy Editor of Chinese Journal of General Surgery and Chinese Journal of Endocrine Surgery
- PhD in Surgery from National University of Singapore, former Lecturer at Harvard University’s Dana-Farber Cancer Institute before returning to China
- Leader of multiple national major projects, including key projects from the National Natural Science Foundation and international cooperation key projects
- Pioneer in the application of liquid biopsy and immunotherapy in breast cancer and initiator of the first consensus guidelines for young breast cancer diagnosis and treatment in China
- Recipient of the “National Famous Doctor – Outstanding Style” honor in 2020 by People’s Daily
- Specializes in the diagnosis, surgery, and comprehensive treatment of breast cancer, particularly in high-difficulty breast-conserving surgery, individualized precision treatment of young and triple-negative breast cancer.
