Leaping first-line therapy with nafulizumab and second-line therapy for esophageal squamous cell carcinoma

Recently, nevulizumab has been widely reported in the field of immunity After becoming the first immunosuppressant to enter the Chinese market in 2018, navurizumab has become the first PD-1 inhibitor to achieve head and neck squamous cell carcinoma indications in the Chinese market In the field of esophageal cancer with Chinese characteristics, navurizumab also announced the action-3 for the first time at the recent 2019 ESMO annual meeting (later called att-3) this is a satisfactory answer Based on the results of att-3 study, in the second-line treatment of unresectable advanced or recurrent esophageal squamous cell carcinoma, navurizumab has become the first immunosuppressant in the world that has been proved to improve the OS of PD-L1 non selective population Recently, the reporter invited Professor Xu Jianming, Department of digestive oncology, the fifth medical center of the General Hospital of the people's Liberation Army, to have an in-depth interpretation of the study Before that, he said, there had been no clinical breakthrough in the field of esophageal squamous cell carcinoma for a long time Att-3 is the world's first phase III clinical study for esophageal squamous cell carcinoma It is not only large in sample size, but also designed mainly for Asian population It provides a well tolerated single drug regimen for patients with advanced esophageal squamous cell carcinoma who usually have poor prognosis This is of epoch-making significance for the number of cases accounting for 50% of the world and more than 90% of esophageal cancer patients in China It is expected that immunotherapy with nevulizumab will benefit more local patients as soon as possible Att-3 is a multicenter, randomized, open label, global phase III clinical study involving 419 patients with previously refractory or intolerable advanced or recurrent esophageal squamous cell carcinoma (ESCC) treated with fluoropyrimidine and platinum-containing drugs The patients in the study group (regardless of the expression of PD-L1) were randomly assigned to receive wuliutab or chemotherapy (docetaxel or yew) Alcohol), the primary end point of the study was overall survival (OS) 1 Regardless of the expression level of PD-L1, patients can achieve OS benefits The median survival time (MOS) was 10.9 months (95% CI: 9.2-13.3) in the nafulizumab group and 8.4 months (95% CI: 7.2-9.9) in the chemotherapy group In the entire study population, the risk of death was reduced by 23% in the nafulizumab group with a 2.5-month prolongation of MOS In PD-L1 positive (≥ 1%), nafulizumab reduced the risk of death compared with chemotherapy (HR = 0.69, 95% CI: 0.51-0.94) In PD-L1 negative (< 1%), the advantage still exists (HR = 0.84, 95% CI: 0.62-1.14) Total survival data The 12-month survival rates of the two groups were 47% and 34%, and the 18-month survival rates were 31% and 21%, respectively This means that at 12 and 18 months, there were more survivors in the nevulizumab group, and one in every two patients survived one year after treatment Based on this result, in the second-line treatment of unresectable advanced or recurrent esophageal squamous cell carcinoma, navurizumab has become the first immunosuppressant in the world that has been proved to improve the OS of PD-L1 non selective population 2 Once effective, the effect will last The long-lasting effect of immunotherapy is also reflected in esophageal cancer In the att-3 study, the objective response rate (ORR) of the two groups was similar (19% vs 22%) Although the orr of the two groups was close, the two groups brought more lasting response The data showed that the median duration of remission (mdor) was nearly twice as long (6.9 vs 3.9 months) in the response group as in the chemotherapy group By the time of data statistics, 7 patients in the nevulizumab group still had continuous remission, while 2 patients in the chemotherapy group had significant "tail effect" of immunotherapy Median duration of remission 3 Significant reduction of adverse reactions In terms of safety, the overall incidence of treatment-related adverse events (traes) was significantly lower in the nafulizumab group than that in the chemotherapy group (66% vs 95%), and the incidence of 3-4-level traes was 3 times lower than that in the chemotherapy group (18% vs 63%), and it was generally controllable and reversible 4 Significant improvement in quality of life In addition, an exploratory analysis of patients' reported outcomes (pro) showed that nafulizumab significantly improved the quality of life of patients compared with chemotherapy Pro exploratory analysis The 2019 edition of CSCO esophageal cancer diagnosis and treatment guide released in April this year recommended nevulizumab This is the first time in China to propose immunotherapy represented by nevulizumab as the recommended scheme for the second-line and above treatment of metastatic esophageal cancer One of the evidences for its renewal is the results of phase II treatment-1 clinical study Nafulizumab is used in patients with advanced esophageal squamous cell carcinoma who are failed or intolerable to be treated with fluorouracil / platinum / paclitaxel drugs The efficacy is significant and the safety is controllable and tolerable In addition to providing further guidance, the results of the published att-3 study will also have a significant impact on the clinical practice of esophageal cancer in China On the one hand, China has a large number of patients with esophageal cancer, especially esophageal squamous cell carcinoma, accounting for more than 90% In addition, there is a lack of treatment means Chinese clinicians pay great attention to the att-3 research, which specializes in esophageal squamous cell carcinoma and accounts for 96% of patients in Asia On the other hand, there are ethnic differences in the therapeutic effect of immunotherapy Professor Xu Jianming said, "in terms of etiology, reflux esophagitis is the main cause of esophageal cancer in western countries; in Asian countries, especially in China, unhealthy eating habits and smoking are the main causes of esophageal cancer Therefore, there are some differences between the eastern and Western esophageal cancer at the molecular level, and often some gene variations at the molecular level come from gene variations in the immune pathway, which may lead to different therapeutic effects of the same treatment method in the eastern and Western esophageal cancer population " The att-3 research covers the Asian population in an all-round way, which can be called customized for Eastern countries This study confirmed that as a second-line single drug therapy, nafulizumab can bring survival benefits without differentiation of PD-L1 expression level, which undoubtedly enhanced the confidence of Chinese doctors, and also brought more enlightenment for the future Oriental exploration of immunotherapy The obvious survival benefits of second-line drugs is a breakthrough in esophageal cancer, but the longer survival prognosis and better quality of life are always the common pursuit of researchers, clinicians and patients "It can be quite clear that as a second-line treatment for esophageal squamous cell carcinoma, nafulizumab is a treatment plan that can change the authoritative guidelines at home and abroad, and it is expected that NCCN guidelines will soon recommend it." Professor Xu Jianming said, "in the future, the application of immunotherapy in esophageal cancer is bound to step forward, such as exploring in the first-line treatment and new adjuvant treatment Although the results of first-line combined chemotherapy are still in the process of "incubation", the results are very worthy of expectation " In fact, a global phase III study, codenamed checkmate-648, is in full swing 939 patients with esophageal squamous cell carcinoma are planned to be included in the study, aiming to evaluate the difference in efficacy and safety of nivo + IPI, nivo + chemotherapy and chemotherapy as the first-line treatment for esophageal squamous cell carcinoma patients It is expected to be completed in December 2021 Recently, the results of a phase III clinical study named checkmate-9la published by BMS also attracted the attention of the author This study confirmed that the combination of dual immunotherapy (nivo + IPI) has reached the main end point of improving OS in the first-line treatment of NSCLC, marking the milestone new progress of the combination of "Gemini" immunotherapy of PD-1 mAb + CTLA-4 mAb again This good news indirectly injected confidence into the clinical research of dual immunotherapy for esophageal cancer, and also made us more looking forward to seeing nevulieu As a first-line therapy, the combination of McAb can improve the survival of patients with OS and PFS Professor Xu Jianming said, "we have reason to believe that the combined immunotherapy program has great hope to enter the ranks of the first-line treatment of esophageal cancer At the same time of continuous progress in drug research and development and medical technology, we hope that with the accelerated review and approval of innovative drugs, innovative immunotherapy can benefit the majority of esophageal cancer patients in China as soon as possible "