Preface
In 2015, the world's first anti-programmed death receptor 1 (PD-1) monoclonal antibody for the treatment of advanced renal cell carcinoma (RCC) was successfully announced, which not only opened the door to immunotherapy for advanced kidney cancer, but also gave rise to a series of competitive waves of anti-PD-1 drugs. Unfortunately, in this international race for the research and development of immunotherapy drugs in the field of advanced RCC, China has been lacking its own "blade".
Until 2023, the wheel of history has turned to a new turning point, and toripalimab has shown excellent efficacy in the RENOTORCH study, bringing new hope to domestic patients with advanced RCC. On April 7, 2024, toripalimab was approved by the National Medical Products Administration (NMPA) and officially landed on the clinical frontline, making it the first target-immune combination regimen for the first-line treatment of advanced RCC in China. On this opportunity, Yimaitong had a conversation Chinese with Academician Zhang Xu from the General Hospital of the People's Liberation Army, Professor Wei Qiang from West China Hospital of Sichuan University, and Professor Xue Wei from Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine to discuss the far-reaching impact of the approval of toripalimab on the treatment process of advanced kidney cancer in China.
To help Chinese RCC patients survive and benefit, toripalimab leads a new era of first-line target-free combination
Yimaitong: The treatment of advanced RCC has undergone many changes from the early cytokine era to the present, could you please share with us how the progress of treatment methods has improved the overall survival of patients with advanced RCC, and what is the significance of the approval of toripalimab for the treatment of patients with advanced RCC in mainland China?
Academician Zhang Xu
Overall, the survival rate of patients with different stages of renal cancer varies greatly, with the current five-year survival rate of 93 percent after surgery for patients with localized cancer, but as low as 18 percent for patients with distant metastases [1]. In addition, patients with advanced RCC can be divided into three groups: low-risk, intermediate-risk, and high-risk, according to the criteria of the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC), and although the median overall survival (OS) of low-risk patients can reach 30 months, the median OS of intermediate-risk patients is only 14 months, and the median OS of high-risk patients is only 5 months [2].
In the 90s of the 20th century, treatment options for advanced renal cancer, including interferon, interleukin, and chemotherapy, did not bring significant survival benefits to patients [3]. Since 2005, advanced RCC has entered the era of targeted therapy, and the median survival time after first-line targeted therapy can be extended to 22 months [4], which has also become the main treatment for advanced kidney cancer in mainland China. In the era of immunotherapy, patient survival has been further improved compared with the targeted monotherapy period [3, 4].
In recent years, with the continuous updating of the data of large-scale first-line target-immune combination studies of mRCC at home and abroad, the target-free combination regimen has become the first-line standard treatment for patients with advanced mRCC [5], and has become an indispensable part of the systemic treatment of advanced kidney cancer. However, unfortunately, there has been no immune drug approved for kidney cancer indication in China before, and the approval of toripalimab will bring international first-line treatment options to Chinese patients with advanced RCC, leading China's advanced RCC treatment into a new era of target-immune combination.
PFS set a new world record, and toripalimab broke through in the field of RCC
Yimaitong: The approval of toripalimab represents the successful entry of a domestic drug into the field of advanced RCC treatment, from the perspective of clinical research, how does the RENOTORCH study perform in international data?
Professor Wei Qiang
With the continuous development of innovative drugs, the exploration of immunotherapy combined with targeted therapy in the first-line treatment of advanced kidney cancer continues to be explored. In the KEYNOTE-426 study, which explored the efficacy of pembrolizumab in combination with axitinib versus sunitinib in the first-line treatment of advanced renal cancer, pembrolizumab plus axitinib extended median progression-free survival (PFS) to 16 months in intermediate- and high-risk patients at 43 months follow-up (11 months in the sunitinib arm, HR = 0.68)[6]. The JAVELIN Renal 101 study also achieved similar results in advanced renal cancer, with avelumab plus axitinib prolonging median PFS to 13.9 months compared with sunitinib in the first-line treatment (8.5 months in the sunitinib arm, HR = 0.67) [7].
The RENOTORCH study of toripalimab in combination with axitinib is a multicenter, randomized, open-label, active-controlled Phase III clinical study with a primary endpoint of PFS as assessed by an independent review committee (IRC). The findings were published in the journal Annals of Oncology in 2023 (Impact Factor: 50.5) [8].
In the intention-to-treat (ITT) set, the median PFS of toripalimab plus axitinib and sunitinib was 18.0 (95% CI 15.0-NE) and 9.8 (95% CI 8.3-13.8) months, respectively, and the PFS of toripalimab plus axitinib was significantly better than that of the sunitinib group, nearly twice that of the sunitinib group, and the risk of disease progression or death on imaging was reduced by 35% (HR = 0.65, 95% CI). 0.490-0.864）[8]。 From the perspective of PFS values, the improvement of toripalimab combined with axitinib on patients was better than the results of previous similar studies, setting a new world record.
There was a trend towards PFS benefit in all subgroups, with toripalimab contributing to improvement in the entire population
Yimaitong: For advanced kidney cancer, risk stratification of IMDC is usually used to predict prognosis and choose treatment options. Can you describe which patients are likely to benefit most from first-line target-free combination therapy?
Professor Xue Wei
At present, domestic and foreign guidelines recommend first-line treatment regimens based on the IMDC score of patients, and the target-free combination regimen is preferentially recommended for medium- and high-risk patients. We note that the RENOTORCH study of toripalimab plus axitinib included 421 patients, of whom approximately eight were intermediate-risk patients and about two were high-risk patients.
A subgroup analysis of PFS benefit showed a trend in the PFS benefit of toripalimab plus axitinib regardless of the patient's IMDC risk level at baseline, the presence of distant metastases, the number of organs metastasized, and the presence or absence of brain metastases.
In addition, the objective response rate (ORR) of toripalimab plus axitinib was 56.7% in the ITT set, as assessed by IRC. Among them, the ORR rates of IMDC intermediate-risk and high-risk patients were 56% and 59%, respectively, which were consistent with the results of the ITT set. The results confirmed that patients were treated with toripalimab in combination with axitinib in response to a good response regardless of the IMDC risk level at baseline [8].
With full expectations, toripalimab has a long way to go in the future
Yimaitong: toripalimab has been successfully approved for 8 indications in China so far, becoming a "polygon warrior" in the field of anti-tumor. From a urologic oncology perspective, what are your expectations for toripalimab?
Academician Zhang Xu
Overall, immunotherapy has become a hot topic in anti-tumor research, and many clinical application results have been achieved. In terms of mechanism, immunotherapy has a wide range of application prospects, which is illustrated by the wide indication layout of toripalimab. For urological tumors, toripalimab can be used not only for the first-line treatment of advanced RCC, but also for the second-line scenario of advanced urothelial carcinoma, and there is no need to detect the expression of PD-1 in patients, which can bring hope for survival to more patients. In the future, we expect that immunotherapy, represented by toripalimab, can play a greater role in the field of urological oncology.
Professor Wei Qiang
At present, there are a variety of treatment methods for urological tumors, and the birth of each treatment method is good news for patients, especially after the emergence of immunotherapy in recent years, various tumor types actively explore the effectiveness of immunotherapy. Among the three major tumors in urology, urothelial carcinoma, kidney cancer and prostate cancer, urothelial carcinoma and kidney cancer have mature systemic treatment options, and toripalimab has both indications, becoming a convenient and easy-to-use treatment tool in the hands of urologists. It is expected that toripalimab will continue to strengthen its exploration in the future, screen out more patients who may benefit from immunotherapy, and help achieve the goal of "Healthy China 2030".
Professor Xue Wei
In terms of mechanism, immunotherapy drugs represented by toripalimab can enhance the body's immune system function, block the immune escape of tumor cells, and activate T lymphocytes to achieve the purpose of anti-tumor. In recent years, there has been significant progress in exploring strategies for the use of immunotherapy in combination with other treatments, such as chemotherapy, targeted therapy, and radiotherapy. Therefore, as an immunotherapy drug that can be applied to both kidney cancer and urothelial cancer, it is expected that toripalimab can explore more immunological combination methods for urological tumors in the future, and continue to lead China's innovation as a pioneer.
brief summary
The approval of toripalimab this time opens a new door for the treatment of patients with advanced RCC in China, and also pushes the "light of domestic products" to the world stage. This reveals the important role of toripalimab in the treatment of advanced RCC and even urological tumors, and also reflects the power of independent innovation in China. Its success is not only the success of a drug, but also an important victory for China in the global pharmaceutical R&D competition. With the wide clinical application of toripalimab in the future, it is believed that it will shine more brightly in the field of global anti-tumor therapy.
- Academician Zhang Xu -
- Director of the Department of Urology, PLA General Hospital
- Academician of the Chinese Academy of Sciences
- Member of the Faculty of the Chinese Academy of Medical Sciences
- Chairman-elect of the Urology Branch of the Chinese Medical Association
- Chairman of the Urology Branch of Beijing Medical Association
- Deputy Director of Chinese Human Organ Donation Management Center
- Chairman of the Laparoscopic and Robotic Surgery Branch of the Chinese Anti-Cancer Association
- Director of the All-Army Key Laboratory of War Trauma
- Member of the expert group of the Central Health Commission
- Chief scientist of the National High-tech Research and Development Program and major logistics scientific research projects of the whole army, and a leading talent in science and technology of the whole army
- He is the winner of the National Fund for Distinguished Young Scholars and the National Science and Technology Progress Award, enjoys the special allowance of the State Council, and is the founder of laparoscopy and robotics technology in the mainland urology
- Bladder、《微创泌尿外科杂志》等学术期刊主编
- Professor Wei Qiang -
- Chief physician, professor and doctoral supervisor
- Director of the Urology Disease Center and Director of the Department of Urology, West China Hospital, Sichuan University
- Vice Chairman of the Urology Branch of the Chinese Medical Association
- Vice President of the Urology Branch of the Chinese Medical Doctor Association
- Vice Chairman of the Prostate Cancer and Kidney Cancer Committee of the Chinese Society of Clinical Oncology (CSCO).
- Vice Chairman of the Male Genital Oncology Committee of the Chinese Anti-Cancer Association
- Chairman of the Urology Committee of Sichuan Medical Association
- President of the Surgical Robot Branch of Sichuan Medical Doctor Association
- 《中华医学杂志英文版（CMJ）》及Journal of Evidence-Based Medicine编委
- He is a member of the executive editorial board of the Chinese Journal of Urology
- Professor Xue Wei -
- Vice President and Director of the Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine
- Chief physician, professor, doctoral supervisor
- He is a member of the Standing Committee of the Urology Branch of the Chinese Medical Association
- Chairman of the Urology Branch of Shanghai Medical Association
- Director of Shanghai Urology Clinical Quality Control Center
- He is a member of the Standing Committee of the Urology Branch of the Chinese Medical Doctor Association
- Deputy head of the Minimally Invasive Group of the Urology Branch of the Chinese Medical Association
- Vice Chairman of the Urology Branch of the China Association for the Promotion of International Exchange in Health Care
- Vice Chairman of the Urology Committee of the China Primary Health Care Foundation
- He is an executive member of the 37th Council of Shanghai Medical Association
- Vice Chairman of the Urology Committee of Shanghai Anti-Cancer Association
- Vice Dean of the Institute of Medical Equipment and Technology, Shanghai Jiao Tong University School of Medicine
- Shanghai Leading Talent, Shanghai Outstanding Academic Leader, Shanghai Craftsman
- As the first completer, he won the first prize of the Outstanding Scientific Research Achievement Award (Science and Technology) of Colleges and Universities and the first prize of Shanghai Medical Science and Technology Award
bibliography
1. National Institutes of Health. Kidney SEER 5-Year Relative Survival Rates, 2013-2019 2024 [cited 2024-03-26]. Available from: https://seer.cancer.gov/statistics-network/explorer/application.html?site=630&data_type=4&graph_type=5&compareBy=stage&chk_stage_104=104&chk_stage_105=105&chk_stage_106=106&chk_stage_107=107&series=9&sex=1&race=1&age_range=1&advopt_precision=1&advopt_show_se=on&advopt_show_ci=on&hdn_view=1&advopt_show_apc=on&advopt_display=2#resultsRegion1.
2. 中华人民共和国国家卫生健康委员会. 肾细胞癌诊疗指南（2022 年版） 2022 [cited 2024-03-26]. Available from: http://www.nhc.gov.cn/yzygj/s2911/202204/a0e67177df1f439898683e1333957c74/files/71c1a3953bcd42059e1bda2859305cef.pdf.
3. Curti B D. New England Journal of Medicine. 2018, 378(14): 1344-1345.
4. Renal Cancer Group, Urogenital Tumor Professional Committee, Chinese Anti-Cancer Association, et al. Journal of Clinical Urology. 2022, 37(5).
5. European Association of Urology. Renal Cell Carcinoma 2023 [cited 2024-03-13]. Available from: https://uroweb.org/guidelines/renal-cell-carcinoma.
6. Plimack E R, et al. Eur Urol. 2023, 84(5): 449-454.
7. Tomita Y, et al. ESMO Open. 2023, 8(6): 102034.
8. Yan X Q, et al. Annals of Oncology. 2024, 35(2): 190-199.
Edit: Nobody
审校:Kristen
Typesetting: KIKI
Execution: Uni
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