Recently, the results of the results of the RENOTORCH study of the PD-1 immunotherapy drug teripulimab combined with axitinib combined with vislitinib in the first-line treatment of patients with unresectable or metastatic renal cell carcinoma (RCC), jointly led by Professor Guo Jun of Peking University Cancer Hospital and Professor Huang Yiran of Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine. The results showed that compared with sunitinib monotherapy, teripulimab combined with axitinib first-line treatment of patients with advanced RCC could significantly improve progression-free survival (PFS) and improve the objective response rate (ORR) of patients, and the safety profile was good, with a median PFS of 18.0 months, which was nearly 2 times longer, setting a new record for first-line immunotargeted therapy benefits for advanced kidney cancer.
It is particularly worth mentioning that the above research results were reported orally by Professor Sheng Xinan of Peking University Cancer Hospital at the recent annual meeting of the European Society of Medical Oncology (ESMO), and the full text was simultaneously awarded the official journal of ESMO “Oncology Yearbook”. It is reported that Sheng Xinan and Professor Zhai Wei of Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine are the co-corresponding authors of the article, Yan Xieqiao of Peking University Cancer Hospital, Ye Mingjiao of Hunan Cancer Hospital and Professor Zou Qing of Jiangsu Cancer Hospital are co-first authors.
Professor Sheng Xinan of Peking University Cancer Hospital gave an oral speech at the meeting (Photo provided by interviewee)
Patients with advanced kidney cancer benefit
Kidney cancer is the third most common malignant tumor of the urinary system in the world, and RCC accounts for 80%~90% of all kidney cancer cases. According to statistics, in 2020, the number of cases of kidney cancer worldwide was 431,000, and the number of deaths was 179,000. In 2022, there were about 77,000 new cases and 46,000 deaths of kidney cancer in China.
Among them, about 1/3 of kidney cancer patients have distant tumor metastasis at the time of initial diagnosis, while 20%~50% of localized patients still have distant tumor metastasis after nephrectomy. Based on the risk classification of the International Consortium of Metastatic Renal Cell Carcinoma Databases, the median overall survival (OS) of patients with low-, intermediate-, and high-risk metastatic RCC who received antivascular targeted therapy was 35.3, 16.6, and 5.4 months, respectively.
The RENOTORCH study is the first pivotal phase III study of immunotherapy for advanced kidney cancer in China, conducted in 47 clinical research centers nationwide, aiming to evaluate the efficacy and safety of teripulimab combined with axitinib first-line treatment in patients with high-risk unresectable or metastatic RCC.
Enrollment initiated in August 2020 and randomized 421 patients with intermediate- to high-risk unresectable or metastatic RCC who had not previously received any systemic therapy to teripulimab plus axitinib (n=210) or sunitinib monotherapy (n=211) until disease progression or intolerable toxicity. The primary endpoints were PFS assessed by an independent review committee (BIRC), and secondary endpoints included investigator-assessed PFS, IRC or investigator-assessed ORR, duration of response (DOR) and disease control rate (DCR), OS, and safety.
As of March 31, 2023, mid-term analysis data from the RENOTORCH study showed that the use of teripulimab plus axitinib first-line treatment of patients with unresectable or metastatic RCC significantly increased progression-free survival (PFS) by nearly 2-fold and reduced the risk of disease progression or death by 34% compared with sunitinib monotherapy, with benefits in all subgroups. Unlike previous studies of the same type that included patients at all risk levels, this study only included intermediate- and high-risk patients, and still achieved the longest median PFS of the same type of studies reported to date; At the same time, the ORR was significantly increased by 56.7%, and the combination treatment group showed a longer lasting sustained remission of the disease. There was a clear trend of OS benefit, with a 39% reduction in the risk of death; The safety was manageable and well tolerated, and no new safety signals were identified.
Fill the gap of first-line immunotherapy in Chinese groups of renal cell carcinoma
“RENOTORCH, as the first phase III clinical study to validate the combination in the Chinese kidney cell carcinoma population, will fill the gap of first-line immunotherapy for Chinese groups of renal cell carcinoma. This is a solid step forward in the prevention and treatment of renal cell carcinoma in China, and it also shows the national competitiveness of Chinese researchers and China’s original research products, and highlights the strength of the country at the front end of academia. Zhang Xu, an academician of the Chinese Academy of Sciences, said.
Professor Guo Jun of Peking University Cancer Hospital believes that the treatment of advanced kidney cancer, from the era of cytokines to targeted therapy to immunotherapy, has entered the era of targeted combined immunotherapy. Immunocombination therapy has become a first-line standard regimen for advanced stage recommended by authoritative guidelines at home and abroad, but there is still a lack of high-level evidence-based and treatment regimens based on Chinese population.
As the first targeted immunotherapy study for kidney cancer in China, RENOTORCH establishes a high-level evidence-based study for Chinese groups and diagnosis and treatment background, and provides a new treatment plan for patients with advanced kidney cancer in China. Teripulimab is a domestically produced drug that is unique in terms of accessibility. “The success of RENOTORCH’s research can stimulate the development of similar research and product development in China, and play the power of role models to promote the continuous advancement of the health cause.” Guo Jun said.
“First-line therapy is a key treatment opportunity for patients with advanced kidney cancer, and prolonging survival and expanding the population of beneficiaries are the key treatment goals at this stage. The results of the RENOTORCH study have refreshed the benefit of PFS in targeted immune therapy for advanced kidney cancer, while bringing unexpected surprises at multiple key endpoints. Professor Huang Yiran of Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine said, “The success of this study means that the field of kidney cancer treatment in China is expected to usher in the first ‘immune + targeted’ combination therapy, leading China’s kidney cancer treatment into the era of targeted treatment.” ”
It is understood that teripulimab injection, as the first domestic PD-1-targeted monoclonal antibody drug approved for marketing in China, has been supported by major national science and technology projects, and has carried out more than 40 clinical studies initiated by the company covering more than 15 indications worldwide. Key regulatory clinical studies underway or completed evaluate the safety and efficacy of teripulimab in multiple tumor types, including lung, nasopharyngeal, esophageal, gastric, bladder, breast, liver, kidney and skin cancers. Based on the positive results of the RENOTORCH study, the National Medical Products Administration (NMPA) has officially accepted the new indication application for teripulimab combined with axitinib for first-line treatment of patients with unresectable or metastatic RCC in July this year.
“The success of today’s RENOTORCH study means that teripulimab can help clinicians bring life to patients with advanced first-line kidney cancer, and also demonstrates the strong strength of original research in China.” We hope that the innovative therapy of teripulimab combined with axitinib can enter clinical application as soon as possible and benefit patients with advanced kidney cancer in China.” Li Cong, co-CEO of Junshi Biologics, said. (Source: Zhang Siwei, China Science News)
Related paper information:https://doi.org/10.1016/j.annonc.2023.09.3108
