Professor Ye Dingwei: Immunotherapy is out of the circle and solves the problem of urothelial cancer

Editor's Note When the study of adjuvant therapy for muscle-invasive urothelial carcinoma (MIUC) was experiencing several setbacks, nivolumab came with the CheckMate-274 study, illuminating the dawn of adjuvant therapy for MIUC
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Coinciding with the conclusion of the 2022 CSCO Guideline Conference, Yimaitong was honored to invite Professor Ye Dingwei, Vice President of Fudan University Affiliated Cancer Hospital, to analyze the advantages of immunotherapy in the adjuvant treatment of MIUC, and look forward to the future development trend of immunotherapy for urothelial carcinoma
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Expert introduction Prof.
Ye Dingwei's DFS doubled in the dawn of spring.
The "nano" hand show is amazing.
For patients who have undergone radical resection, Prof.
Ye Dingwei believes that there are two major needs: to further improve the cure rate and disease-free survival rate, and to reduce the risk of recurrence and metastasis of patients.
Further improve the quality of life of patients after surgery and reduce the impact of surgery on patients.
Postoperative adjuvant therapy can prolong disease-free survival (DFS), metastasis-free survival (MFS) and overall survival (OS) of patients, while previous chemotherapy There is still a lack of high-level evidence on the clinical benefit of the protocol, and there are major limitations
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"So we have never stopped exploring, and are always working hard to find more effective adjuvant treatments
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" Professor Ye Dingwei said, "Immune checkpoint inhibitors have given us a lot of expectations, but we have been waiting until the CheckMate- The positive results of the 274 study have only strengthened our confidence
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” As the first phase III study with positive results of adjuvant immunotherapy after MIUC, Prof.
Ye Dingwei said that the results of the CheckMate-274 study are of great significance
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Immunotherapy has been successfully used in the adjuvant treatment of high-risk MIUC postoperatively, providing a new idea for clinical diagnosis and treatment
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In the randomized patient (ITT) population, the median DFS of the nivolumab group was twice that of the control group (22.
0 months vs.
10.
9 months), with a 30% reduction in the risk of recurrence or death in PD-L1 expression ≥ In 1% of patients, nivolumab reduced the risk of disease recurrence or death by 47% compared with the control group In the ITT population, the nivolumab group prolonged median extraurethral recurrence-free survival compared with the control group Patients with PD-L1 expression ≥ 1% benefited more significantly 1
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Table 1 A quick overview of the CheckMate -274 study data Currently, immunotherapy for the adjuvant treatment of MIUC has been recommended by major domestic and foreign authoritative guidelines.
Based on the CheckMate -274 study, nivolumab will be awarded the CSCO guideline for the diagnosis and treatment of urothelial carcinoma in 2021 The class II category 1A recommendation for postoperative adjuvant immunotherapy for muscle-invasive bladder urothelial carcinoma and upper tract urothelial carcinoma
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Professor Ye Dingwei said that the inclusion of nivolumab in the CSCO guidelines is of great value to the adjuvant treatment of MIUC
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Table 2 2021 CSCO Guidelines for the Diagnosis and Treatment of Urothelial Carcinoma Recommendations for adjuvant therapy after MIUC In August 2021, nivolumab was approved by the US FDA for adjuvant urothelial carcinoma (UC) patients with high risk of recurrence after radical resection treatment, regardless of whether the patient had previously received neoadjuvant chemotherapy, nodal involvement, or PD-L1 expression status
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The approval of nivolumab is expected to become a new standard of adjuvant therapy in the future while enriching the treatment options for patients and physicians
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Fangxingwei Ai has "incorporated" into the layout of multiple treatment tracks for urothelial cancer.
"Immunotherapy is an important track and direction for future research on urothelial cancer," said Professor Ye Dingwei
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The promising prospects of immunotherapy are related to factors such as strong immunogenicity and high PD-L1 expression level in urothelial carcinoma 2
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With the in-depth exploration of immunotherapy combined with chemotherapy and targeted drugs, the application of immunotherapy will gradually cover from the late stage to the earlier stage, which is expected to rewrite the existing treatment layout of UC
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At present, clinical studies of immunotherapy represented by nivolumab have achieved second-line, first-line, and perioperative treatment for locally advanced or metastatic bladder urothelial carcinoma, as well as infusion therapy for non-muscle-invasive urothelial carcinoma.
comprehensive layout
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Among them, the NABUCCO study 3 and BLASST-1 study 4, which explored the use of nivolumab combined with ipilimumab/combination chemotherapy for neoadjuvant treatment of UC, have achieved good results, suggesting that neoadjuvant immunotherapy will protect the future.
Bladder therapy brings possibilities
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Table 3 Nivolumab’s deployment in the field of UC came later Immunotherapy became the fourth method of bladder-preserving treatment for UC Radical cystectomy (RC) is the standard treatment for high-risk non-muscle-invasive bladder cancer in patients with MIUC and BCG failure However, there are many patients who are not suitable for or refuse RC because of their underlying diseases or the decline of postoperative quality of life
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Therefore, bladder preservation therapy balances tumor control and quality of life to a certain extent, and becomes an alternative and supplement to RC
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 Talking about bladder preservation treatment, Professor Ye Dingwei said that the 'sandwich' method was used in the past, that is, surgery + systemic chemotherapy + radiotherapy
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In the era of immunotherapy, after PD-1 inhibitors represented by nivolumab were used in neoadjuvant immunotherapy for MIUC, the pathological complete response rate (pCR) was significantly improved, which further promoted the concept of bladder preservation
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The breakthrough made by immunotherapy research has also made it the fourth bladder-preserving treatment after surgery, radiotherapy and chemotherapy
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 However, due to the lack of treatment standards and norms in practical clinical applications, comprehensive bladder-preserving therapy has been facing many challenges
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In 2022, "China's Consensus on Multidisciplinary Diagnosis and Treatment of Bladder Conservation Treatment for Bladder Cancer"5 (hereinafter referred to as the "Consensus") came into being, and put forward normative guidelines for bladder preservation treatment
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The consensus pointed out that bladder-preserving treatment of bladder cancer requires the collaborative diagnosis and treatment of urology, medical oncology, radiotherapy, pathology, and radiology
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 "The treatment of solid tumors has developed so far, and we have confirmed that a single department is far inferior to the advantages of multidisciplinary comprehensive diagnosis and treatment, and cannot maximize the value of treatment
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" Professor Ye Dingwei said, "Whether it is for early, middle or late stage MDT can significantly improve the cure rate and survival rate of patients with 100,000 patients
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Especially in the era of immunotherapy, we need to vigorously promote the concept of MDT, so that the DFS and OS of patients can be greatly improved
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References: 1.
Galsky MD, Witjes JA, Gschwend JE, et al.
Disease-free survvial with longer follow-up from the phase 3 CheckMate 274 trial of adjuvant nivolumab in patients who underwent surgery for high-risk muscle-invasive urothelial carcinoma, Poster presentation at the Society of Urologic Oncology (SUO) annual meeting.
December 1-3, 2021.
2.
Lawrence MS et al, Nature 2013 Jul 11;499(7457):214-218.
3.
Annals of Oncology (2021) 32 ( suppl_5): S1283-S1346.
10.
1016/annonc/annonc741.
4.
Shilpa Gupta, et al.
Biomarker analysis and updated clinical follow-up from BLASST-1 (Bladder Cancer Signal Seeking Trial) of nivolumab, gemcitabine, and cisplatin in patients with Muscle-invasive bladder cancer (MIBC) undergoing cystectomy.
Journal of Clinical Oncology 2022 40:6_suppl, 528-528.
5.
Urological Oncology Collaborative Group of China Cancer Hospital.
Chinese consensus on multidisciplinary diagnosis and treatment of bladder cancer for bladder preservation[J].
Chinese Journal of Oncology , 2022, 44(3):209-218.
Editor: Bing Xin Typesetting: Uni Execution: Quinta