The 2023 European Society for Medical Oncology (ESMO) Congress opened grandly in Madrid, Spain on October 20. Top global oncology experts gathered to discuss and share the latest international advances in cancer research and treatment techniques. Professor Shun Lu and his team from Shanghai Jiao Tong University Affiliated Thoracic Hospital brought a heavyweight study on Chemotherapy-Induced Anemia (CIA) to the 2023 ESMO Late-breaking Abstract (LBA) session, which is a pivotal event at the ESMO annual meeting, providing essential insights for clinical practice. “Oncology Frontier” had the privilege of inviting Professor Shun Lu to share the relevant content at the ESMO Congress.
“Oncology Frontier”: Chemotherapy-Induced Anemia (CIA) is a common adverse reaction in cancer treatment. First, could you please share the current status of CIA management in China and what clinical needs remain unmet?
Professor Shun Lu: Some severe adverse reactions caused by chemotherapy are, in fact, significant barriers to the normal use of chemotherapy. Common examples include short-term toxicities of chemotherapy, such as gastrointestinal toxicity. Medium to long-term toxicities include hematologic toxicity, which comprises short-term neutropenia, typically occurring 10 to 40 days after chemotherapy. With the advent of G-CSF, neutropenia has seen substantial improvement. The second category is medium to long-term hematologic toxicity, mainly affecting the erythroid lineage, affecting hemoglobin levels, and the megakaryocytic lineage, which influences platelet counts. Regarding treatment strategies, managing erythroid lineage reduction mainly involves two approaches: one is for acute anemia, and the preferred treatment is blood transfusion. However, the proportion of CIA patients who require blood transfusions is relatively low, and China faces a shortage of blood resources. Additionally, the use of blood products may lead to iatrogenic infections (mainly viral hepatitis in China). Another treatment approach is the most commonly used recombinant human erythropoietin (rhEPO) worldwide. Amgen in the United States was the first to develop rhEPO, and many domestic companies have also developed similar products. However, these products require injections, whether intramuscular, subcutaneous, or intravenous, all administered in the hospital. Currently, in many large tertiary hospitals, including ours, most patients come from different regions and return home after chemotherapy, making the use of injectable drugs relatively cumbersome. Although everyone knows that anemia needs intervention and management, the proportion of CIA patients, especially those with mild to moderate anemia, who actually receive treatment in China is not very high. So we urgently need convenient and straightforward treatment options, especially oral medications that patients can take home. This way, we can ensure that these patients receive timely treatment for anemia, which is essential to maintain the required hemoglobin levels for subsequent chemotherapy, ensuring both the patient’s ability to endure an adequate dose of chemotherapy and the effectiveness of chemotherapy itself. In fact, we are well aware that without receiving an adequate dose of chemotherapy, not only does it reduce the intensity of chemotherapy for patients, but it also leads to a decrease in the overall survival rate. Additionally, anemia itself limits a patient’s ability to function, significantly affecting their quality of life.
“Oncology Frontier”: In this year’s ESMO Congress, you shared a Phase III clinical study (LBA96) on the use of Roxadustat to treat non-myeloid cancer CIA. Could you please introduce the clinical design and main results of this study?
Professor Shun Lu: In our treatment of anemia, oncologists often learn from nephrologists because we know that renal anemia is the most common and severe type of anemia. Therefore, our treatment, including erythropoiesis-stimulating agents, initially started with renal anemia. Roxadustat is an orally administered preparation developed by the American company FibroGen. It works by reversibly inhibiting prolyl hydroxylase (PHD), stabilizing hypoxia-inducible factor (HIF) levels, activating downstream target genes related to red blood cell production, promoting erythropoietin (EPO) generation, and increasing EPO receptor expression. On the other hand, it promotes transferrin and transferrin receptor expression, downregulates hepcidin levels, increases iron transport, and enhances red blood cell production, thereby raising the patient’s hemoglobin levels. Our study compared the efficacy of standard rhEPO and Roxadustat in treating anemia in solid tumors. Roxadustat has already been approved in China for renal anemia, so we conducted this head-to-head trial against the background of renal anemia, examining two existing treatment methods for chemotherapy-induced anemia (CIA).
“Oncology Frontier”: In the course of this study, what aspects of the Roxadustat treatment group stood out to you, and what are the considerations for using Roxadustat?
Professor Shun Lu: During the course of this drug study, we experienced the COVID-19 pandemic in China, and the pandemic actually left a deeper impression on me regarding this research. Because Roxadustat is an orally administered medication, we could easily deliver it to patients through a convenient delivery system. RhEPO, on the other hand, requires injection. Due to pandemic control measures, patients found it challenging to receive timely treatment with rhEPO. This situation highlights the convenience of oral medications and the strong demand for their use, especially during special times like the pandemic. We also know that when treating cancer-induced anemia with rhEPO, if patients have iron deficiency, iron supplementation is required. Roxadustat can regulate iron metabolism, reducing the need for additional iron supplements, which further enhances its convenience. These two aspects left a deep impression on me. Overall, Roxadustat’s oral administration is more convenient, and patients are more compliant with it.
“Oncology Frontier”: As the lead researcher of this study, how do you evaluate the study, and what impact do you think this research will have on the management of CIA?
Professor Shun Lu: As the lead researcher of this study, I am very pleased and somewhat proud that this is the first randomized controlled trial using a positive drug as a control. Because, as you know, many studies of rhEPO in solid tumors were compared to placebos, and we conducted a head-to-head study with rhEPO as the control group, with the current results showing that it has met the standard of non-inferiority. We also observed that in some aspects, such as the degree of anemia improvement and the reduction in the number of anemic days, Roxadustat’s values are superior to rhEPO. Of course, as it is a non-inferiority study design, we cannot claim statistical significance, but Roxadustat is at least as good as rhEPO. Therefore, we look forward to its rapid approval by the relevant regulatory authorities in China and hope it will be included in medical insurance as soon as possible. This way, I believe it may change the treatment landscape for cancer patients in China. For patients, taking an oral medication home after chemotherapy is very convenient, and they won’t need to repeatedly visit different hospitals. In contrast, if rhEPO is used for treatment, patients still need to go to the hospital for injections continuously, which is not suitable for cancer patients. In some cases, they may have a decreased white blood cell count during the acute phase, which increases the risk of infection if they spend too much time in public places. So, having an oral medication for anemia treatment at home is a convenient and safe choice for cancer patients. I believe that the availability of this medication not only fills the gap in oral formulations in this regard but also benefits more patients, providing a good and convenient treatment option for anemia in solid tumor patients.
“Oncology Frontier”: This study has already achieved such promising results. What are your plans for the next steps?
Professor Shun Lu: The success of this study firstly reflects the efforts made by the sponsor to extend a drug developed for renal anemia to cancer-induced anemia. Secondly, what we want to do in the future is actively disseminate the research results to our peers so that we can share the achievements of our research with them. Ultimately, it is all for the patients. We hope that through our efforts, cancer-induced anemia patients can receive timely and scheduled treatment, addressing drug accessibility and effectiveness, maximizing convenience for patients, allowing them to lead a normal life without the need for multiple hospital visits.
References:
1. ESMO 2023. Abstract #LBA96.
Professor Shun Lu
Chief Physician, Doctoral Supervisor, Second-level Professor
National Health and Health Outstanding Contribution Young Expert
Shanghai Leading Talent
Outstanding Academic Leader in Shanghai
National Key Project Chief Expert
Recipient of the Special Allowance from the State Council
Director of Shanghai Jiao Tong University School of Medicine Affiliated Thoracic Hospital
Director of the Shanghai Lung Cancer Clinical Medical Center
Director of the Chinese Anti-Cancer Association
Executive Director of the Chinese Society of Clinical Oncology (CSCO)
Vice Chairman of the Heiskell Foundation
Chairman of the DIA China Advisory Committee
Former Chairman of the Shanghai Medical Association Oncology Society
Standing Committee Member of the Chinese Medical Association Oncology Society
Director of the Shanghai Physician Association Oncology Branch
Specialty Training Group Leader
Committee Member of the International Association for the Study of Lung Cancer (IASLC) Publication Committee
Chinese Representative for the American Society of Clinical Oncology (ASCO)
Editor-in-Chief of the Official Journal of the International Association for the Study of Lung Cancer (IASLC), Lung Cancer, and Editor of The Oncologist
Executive Director of the Shanghai Anti-Cancer Association
Vice Chairman of the Precision Medicine Branch of the China Association for Medical Biotechnology
Lead investigator in key projects funded by the Ministry of Science and Technology, the National Major New Drug Innovation Project, 863 Major Project Subproject (2 projects), and the National Natural Science Foundation of China (key projects and general projects).
Recipient of the Chinese Anti-Cancer Association Science and Technology Award First Prize
Recipient of the Shanghai Medical Science and Technology Award First Prize
Recipient of the Huaxia Medical Science and Technology Award Second Prize
Recipient of the Shanghai Science and Technology Progress Award First Prize
Recipient of the Shanghai Jiao Tong University President’s Award
Nominated for the Renxin Doctor Shanghai Outstanding Specialist Physician Award in 2018
Recipient of the “WuXi AppTec Life Chemistry Research Award” in 2021
