Refresh the longest survival period! Toripalimab is approved for first-line treatment of advanced esophageal squamous cell carcinoma

Recently, the anti-PD-1 monoclonal antibody independently developed by a local innovative pharmaceutical companyToripalimab Injection(Tuoyi^® )in combination with paclitaxel and cisplatin(TP chemotherapy)for unresectable locally advanced/recurrent or distant metastatic esophageal squamous cell carcinoma (ESCC)First-line treatment for patientsNew indications approved by State Drug Administration span>(NMPA)Approved. This is also the fifth indication of Toripalimab approved in Chinathe fifth indication, which will bring benefits to Chinese patients with advanced esophageal squamous cell carcinoma. Better survival benefits.

esophageal cancerIt is one of the most common malignant tumors in the digestive tract. According to statistics, in 2020, the number of new cases of esophageal cancer in China will reach 320,000, and the number of deaths will reach 300,000, accounting for more than half of the world’s total. Four ^[1,2]. Esophageal squamous cell carcinoma and adenocarcinoma are the two main histological subtypes of esophageal cancer. Esophageal squamous cell carcinoma is the main subtype in Chinese patients, accounting for about 90% of the overall incidence.^[3].

Although surgery is the best choice for curative treatment of non-metastatic esophageal squamous cell carcinoma, postoperative recurrence often occurs . In addition, because the early symptoms of esophageal cancer are not obvious, most patients are already in the advanced stage when they are first diagnosed. For patients with advanced esophageal squamous cell carcinoma, the current first-line standard treatment is mostly platinum-based chemotherapy, but the clinical benefit is limited, and the 5-year overall survival rate is less than 20%. New drugs and treatment options are urgently needed to prolong the survival of patients period^[4].

The emergence of tumor immunotherapy represented by PD-1 inhibitors is an important factor for the survival of patients with advanced esophageal cancer. Bring about a huge turnaround.

Toripalimab is the first domestically produced PD-1-targeted drug approved for marketing in my country. Monoclonal antibody drugs, independently developed by local innovative pharmaceutical company Junshi Bio, are used for the treatment of various malignant tumors. In 2017, Professor Xu Ruihua’s team carried out a number of early exploratory studies of toripalimab alone or in combination with chemotherapy regimens in the treatment of different malignant tumors, and achieved positive results in the field of ESCC treatment, which provided the basis for subsequent large-scale phase III studies. solid theoretical foundation.

This new indication was approved based on a randomized, double-blind, placebo-controlled, multicenter Phase III clinical trial of JUPITER-06(NCT03829969). The research was jointly carried out by 72 units across the country, including Sun Yat-sen University Cancer Center, Cancer Hospital of Chinese Academy of Medical Sciences, First Affiliated Hospital of Henan University of Science and Technology, and Affiliated Cancer Hospital of Harbin Medical University. Combining a lot of clinical practice experience and basic scientific research, the research team innovatively selected TP chemotherapy in combination with toripalimab in the final program design of JUPITER-06, instead of the “fluorouracil + platinum” program commonly used in Europe and the United States , fully considering the differences in characteristics of Asian ESCC patients and the inclination of previous treatment, in order to customize a “Chinese plan” for Chinese people that is more in line with local clinical practice.

JUPITER-06To compare toripalimab combined with TP chemotherapy Efficacy and safety of TP chemotherapy combined with placebo in first-line treatment of advanced or metastatic esophageal squamous cell carcinoma. The primary endpoint of the trial was progression-free survival (PFS; Blinded Independent Central Reading [BICR], assessed according to Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) and Overall survival(OS), secondary endpoints were investigator-assessed PFS, objective response rate(ORR)< span>and disease control rate(DCR), etc. A total of 514 patients were enrolled in the trial and randomly assigned to the treatment group in a ratio of 1:1(Toripalimab combined with TP chemotherapy)or placebo group(placebo combined with TP chemotherapy).

The research results have been recognized by the international academic community for many times and have been listed in the top oncology journals “Cancer Cell”(Impact factor: 31.743), and presented at the annual meeting of the European Society of Medical Oncology in the form of oral presentation( ESMO 2021)and the Society for Cancer Immunotherapy Annual Meeting(SITC 2021). “Toripalimab + cisplatin + paclitaxel” was included in the 2022 CSCO Guidelines for the Diagnosis and Treatment of Esophageal Cancer this year, and received a Class II recommendation, class IA evidence, “2022 CSCO Immune Examination””Guidelines for the Clinical Application of Point Inhibitors” and received a Class I recommendation.

The results of the study showed that compared with chemotherapy alone, Terry Plimumab combined with TP chemotherapy has resulted in a better survival benefit for more advanced esophageal squamous cell carcinoma patients.

Patients in the toripalimab arm had significantly longer PFS(5.7 months vs 5.5 months), 42% lower risk of disease progression or death(HR=0.58, P<0.0001), The proportion of patients without disease progression within one year was significantly increased(27.8% vs 6.1%), and the median OS of patients was prolonged by half a year(17.0 months vs 11.0 months), the risk of death was reduced by 42%(HR=0.58, P=0.0004).

At the same time, the ORR and DCR of the toripalimab group were also significantly improved, up to 69.3% and 89.1%, suggesting that more patients will shrink their tumors and their symptoms will be relieved after receiving treatment, which will increase their confidence in their follow-up treatment. In terms of safety, toripalimab was added to chemotherapy, and no new safety signal was found.