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50% of patients with muscular invasive urothelial carcinoma will face recurrence after surgery.
However, the adjuvant treatment of combined chemotherapy containing cisplatin in the past is not ideal, and postoperative recurrence has become a high probability event.
Fortunately, at the just-concluded ASCO-GU conference, the adjuvant treatment of urothelial cancer ushered in good news.
A phase III clinical study called CheckMate-274 announced the results for the first time.
Nivolumab (also known as "O drug") adjuvant treatment of muscular invasive urothelial carcinoma prolongs the disease-free survival (DFS) of patients after surgery.
) Nearly 2 times, the risk is reduced by 30%, and the primary research endpoint is reached in all randomized populations and patients with PD-L1 expression ≥1%.
This result has aroused our expectation for the expansion of immunotherapy in genitourinary system tumors and in the field of adjuvant therapy.
Taking this opportunity, Yimaitong has the honor to invite Professor Ye Dingwei, the deputy dean of Fudan University Affiliated Cancer Hospital, to give an in-depth interpretation of the latest developments in urothelial cancer immunotherapy for readers.
Dr.
Ye Dingwei, Chief Physician, Professor, Doctoral Tutor • Associate Dean of Cancer Hospital of Fudan University • Chief Expert of Urological Oncology MDT • Director of Shanghai Urological Oncology Institute • Director of Prostate Cancer Institute of Fudan University • Chinese Anticancer Association Urinary and Male Reproductive Tumor Chairman of the Special Committee (CACA-GU) • Chairman of the Chinese Society of Clinical Oncology (CSCO) Prostate Cancer Expert Committee • Vice Chairman of the Chinese Society of Clinical Oncology (CSCO) Urothelial Cancer Expert Committee • Chinese Society of Clinical Oncology (CSCO) Kidney Vice Chairman of the Cancer Expert Committee • Vice Chairman of the Immunotherapy Expert Committee of the Chinese Society of Clinical Oncology (CSCO) • Chairman of the Urinary Oncology Group (UCOG) of China Cancer Hospital • Standing Director of the Chinese Anti-Cancer Association • Standing Director of the Chinese Society of Clinical Oncology • China Head of the Prostate Cancer Group of the Anti-Cancer Association Urology and Male Reproductive Tumor Committee (CACA-GU) • Deputy Head of the Writing Group of NCCN Kidney Cancer Diagnosis and Treatment Guidelines China Edition • NCCN Asian Consensus Expert Committee on Diagnosis and Treatment of Prostate Cancer, Kidney Cancer, and Bladder Cancer Due to the difficulties of the committee members, 50% of patients with muscular invasive urothelial cancer will relapse after surgery.
Bladder cancer is the most common malignant tumor of the urinary system.
About 90% of bladder cancer is urothelial carcinoma, and about 25% of patients are newly diagnosed as muscular invasive urothelial carcinoma.
Postoperative recurrence is a difficulty that many patients with muscular invasive urothelial carcinoma need to face.
“For patients with urothelial cancer, even after surgical resection, about 50% of patients will still relapse after surgery, or even metastasis.
At present, patients with high risk of recurrence will be given adjuvant treatment after surgery, often Combination chemotherapy containing cisplatin can reduce the rate of tumor recurrence.
However, due to poor liver and kidney function or systemic state, some patients are intolerant to the toxicity of platinum chemotherapy, and the prognosis is relatively poor.
" Professor Ye Dingwei said, "Therefore, for radical treatment For patients who are at high risk of recurrence after cystectomy, their treatment needs are still unmet, and innovative treatment options are urgently needed.
"Reduce recurrence, and immune adjuvant therapy prolongs the postoperative disease-free survival of patients by nearly two times.
At this ASCO-GU conference , Phase III study CheckMate-274 released the results for the first time, and handed in a satisfactory answer for the treatment of urothelial cancer.A total of 709 patients were enrolled in the CheckMate-274 study, and they were randomly assigned to the nivolumab group and the placebo group at a 1:1 ratio.
The primary endpoint of the study was disease-free in all randomized patients and patients with tumors expressing PD-L1 ≥ 1% Survival (DFS), the key secondary endpoints include overall survival (OS), non-urothelial relapse-free survival (NUTRFS) and disease-specific survival (DSS).
According to the first published trial results: the median disease-free survival was nearly doubled.
Among all randomized populations, patients who received nivolumab after surgery had a median DFS nearly doubled compared with the placebo group.
.
Compared with 10.
9 months in the placebo group, 21.
0 months in the nivolumab group.
At the same time, the postoperative disease recurrence rate has been significantly reduced, and the risk is reduced by 30%.
The results of median DFS analysis showed that patients with PD-L1 expression ≥1% benefited more significantly.
Among patients with PD-L1 expression ≥1%, nivolumab can reduce the risk of disease recurrence or death by 47%, nivolumab The median DFS of the group and the placebo group were not reached and 10.
8 months, respectively.
Prolonging non-urothelial recurrence-free survival In all randomized populations, the median NUTRFS of patients treated with nivolumab was more than 2 years, 24.
6 months, and 13.
7 months in the placebo group.
Among patients with tumors expressing PD-L1≥1%, the median NUTRFS of nivolumab and placebo groups were not reached and 10.
9 months, respectively, showing good clinical benefits.
The results of the median NUTRFS analysis showed that adverse reactions were safe and controllable.
The safety of nivolumab is consistent with the safety reported in other solid tumor clinical studies.
The proportions of treatment-related adverse events (TRAEs) in the nivolumab group and placebo group were 77.
5% and 55.
5%, respectively, and the incidence of grade 3 to 4 TRAEs was 17.
9% and 7.
2%, respectively.
"CheckMate-274 is the first and currently the only phase III clinical study that confirmed immunotherapy as an adjuvant treatment for myometrial invasive urothelial carcinoma, and achieved positive results in all random populations and those with PD-L1 expression ≥1%.
"Professor Ye Dingwei explained, "If you let me define, I think this study is the first and currently the only clinical study that proves that immunotherapy is valuable in the adjuvant treatment of bladder cancer, and it has breakthrough significance.
"Across the board, immunotherapy is actively exploring multiple treatment lines for urothelial cancer.
In addition to breakthroughs in the field of adjuvant therapy for urothelial cancer, immunotherapy is also considered to have broad application prospects in multiple treatment lines for bladder cancer.
" This is mainly related to the characteristics of urothelial cancer cells.
Urothelial cancer has strong immunogenicity, its PD-L1 expression level is relatively high, and the tumor mutation burden (TMB) is also high.
Based on the characteristics of these aspects, urothelial cancer is considered to be a “hot tumor”, which is a type of tumor that is relatively “favored” by immunotherapy.
"Professor Ye Dingwei said, "In addition, studies have confirmed that the expression level of PD-L1 is related to the malignancy of urothelial carcinoma, which means that PD-L1 can be used as an indicator of prognosis.
"Higher immunogenicity, higher PD-L1 expression level and higher TMB, the "three highs" characteristics of urothelial cancer have opened up a broad application scenario for the full-line attack of immunotherapy.
At present, more and more Many clinical studies are underway, such as CheckMate-7G8, CheckMate-901, etc.
Immunotherapy represented by nivolumab is expected to bring benefits to patients in many areas of urothelial cancer, including local progression or First-line treatment, second-line treatment, maintenance treatment, adjuvant therapy and perfusion treatment for non-muscular invasive urothelial carcinoma of metastatic urothelial carcinoma.
At the same time, immunotherapy for urothelial carcinoma has also been recognized by many domestic and foreign authoritative clinical guidelines Recommendation: The 2019 European Urology Annual Conference (EAU) Guidelines include immune checkpoint inhibitors in the adjuvant treatment of myometrial infiltrating or metastatic urothelial carcinoma (only applicable to clinical trials) into the guidelines recommendation, and the recommendation level is "strong" "; In the 2019 National Comprehensive Cancer Network (NCCN) Guidelines, PD-1/PD-L1 inhibitors including O drugs are recommended for the treatment of advanced urothelial cancer after platinum-containing chemotherapy.
Line therapy; In 2019, the “Guidelines for the Diagnosis and Treatment of Chinese Urology and Andrology” listed immunotherapy as the recommended treatment for myometrial invasive urothelial carcinoma for the first time. As the domestic leader of the CheckMate-274 study, Professor Ye Dingwei said sincerely at the end of the interview, “I very much look forward to immunotherapy benefiting Chinese patients with genitourinary system tumors as soon as possible and improving their survival and quality of life.
Of course, with the exception of urothelial cancer, Clinical trials of nivolumab in the treatment of kidney cancer and prostate cancer will also be carried out in China, hoping to bring more good news to the clinic.
"Expanded reading In recent years, the exploration of immunotherapy is gradually advancing to the front line, for example, in In the field of adjuvant therapy, immunotherapy has achieved breakthroughs in many tumor types.
Taking nivolumab as an example, it has been confirmed that it has clinically significant efficacy in the adjuvant treatment of four tumor types, including bladder cancer, lung cancer, melanoma, esophageal cancer/gastroesophageal junction cancer.
Front-line exploration of immunotherapy is expected to allow more cancer patients to benefit from survival at an earlier stage and improve the overall prognosis.
However, the adjuvant treatment of combined chemotherapy containing cisplatin in the past is not ideal, and postoperative recurrence has become a high probability event.
Fortunately, at the just-concluded ASCO-GU conference, the adjuvant treatment of urothelial cancer ushered in good news.
A phase III clinical study called CheckMate-274 announced the results for the first time.
Nivolumab (also known as "O drug") adjuvant treatment of muscular invasive urothelial carcinoma prolongs the disease-free survival (DFS) of patients after surgery.
) Nearly 2 times, the risk is reduced by 30%, and the primary research endpoint is reached in all randomized populations and patients with PD-L1 expression ≥1%.
This result has aroused our expectation for the expansion of immunotherapy in genitourinary system tumors and in the field of adjuvant therapy.
Taking this opportunity, Yimaitong has the honor to invite Professor Ye Dingwei, the deputy dean of Fudan University Affiliated Cancer Hospital, to give an in-depth interpretation of the latest developments in urothelial cancer immunotherapy for readers.
Dr.
Ye Dingwei, Chief Physician, Professor, Doctoral Tutor • Associate Dean of Cancer Hospital of Fudan University • Chief Expert of Urological Oncology MDT • Director of Shanghai Urological Oncology Institute • Director of Prostate Cancer Institute of Fudan University • Chinese Anticancer Association Urinary and Male Reproductive Tumor Chairman of the Special Committee (CACA-GU) • Chairman of the Chinese Society of Clinical Oncology (CSCO) Prostate Cancer Expert Committee • Vice Chairman of the Chinese Society of Clinical Oncology (CSCO) Urothelial Cancer Expert Committee • Chinese Society of Clinical Oncology (CSCO) Kidney Vice Chairman of the Cancer Expert Committee • Vice Chairman of the Immunotherapy Expert Committee of the Chinese Society of Clinical Oncology (CSCO) • Chairman of the Urinary Oncology Group (UCOG) of China Cancer Hospital • Standing Director of the Chinese Anti-Cancer Association • Standing Director of the Chinese Society of Clinical Oncology • China Head of the Prostate Cancer Group of the Anti-Cancer Association Urology and Male Reproductive Tumor Committee (CACA-GU) • Deputy Head of the Writing Group of NCCN Kidney Cancer Diagnosis and Treatment Guidelines China Edition • NCCN Asian Consensus Expert Committee on Diagnosis and Treatment of Prostate Cancer, Kidney Cancer, and Bladder Cancer Due to the difficulties of the committee members, 50% of patients with muscular invasive urothelial cancer will relapse after surgery.
Bladder cancer is the most common malignant tumor of the urinary system.
About 90% of bladder cancer is urothelial carcinoma, and about 25% of patients are newly diagnosed as muscular invasive urothelial carcinoma.
Postoperative recurrence is a difficulty that many patients with muscular invasive urothelial carcinoma need to face.
“For patients with urothelial cancer, even after surgical resection, about 50% of patients will still relapse after surgery, or even metastasis.
At present, patients with high risk of recurrence will be given adjuvant treatment after surgery, often Combination chemotherapy containing cisplatin can reduce the rate of tumor recurrence.
However, due to poor liver and kidney function or systemic state, some patients are intolerant to the toxicity of platinum chemotherapy, and the prognosis is relatively poor.
" Professor Ye Dingwei said, "Therefore, for radical treatment For patients who are at high risk of recurrence after cystectomy, their treatment needs are still unmet, and innovative treatment options are urgently needed.
"Reduce recurrence, and immune adjuvant therapy prolongs the postoperative disease-free survival of patients by nearly two times.
At this ASCO-GU conference , Phase III study CheckMate-274 released the results for the first time, and handed in a satisfactory answer for the treatment of urothelial cancer.A total of 709 patients were enrolled in the CheckMate-274 study, and they were randomly assigned to the nivolumab group and the placebo group at a 1:1 ratio.
The primary endpoint of the study was disease-free in all randomized patients and patients with tumors expressing PD-L1 ≥ 1% Survival (DFS), the key secondary endpoints include overall survival (OS), non-urothelial relapse-free survival (NUTRFS) and disease-specific survival (DSS).
According to the first published trial results: the median disease-free survival was nearly doubled.
Among all randomized populations, patients who received nivolumab after surgery had a median DFS nearly doubled compared with the placebo group.
.
Compared with 10.
9 months in the placebo group, 21.
0 months in the nivolumab group.
At the same time, the postoperative disease recurrence rate has been significantly reduced, and the risk is reduced by 30%.
The results of median DFS analysis showed that patients with PD-L1 expression ≥1% benefited more significantly.
Among patients with PD-L1 expression ≥1%, nivolumab can reduce the risk of disease recurrence or death by 47%, nivolumab The median DFS of the group and the placebo group were not reached and 10.
8 months, respectively.
Prolonging non-urothelial recurrence-free survival In all randomized populations, the median NUTRFS of patients treated with nivolumab was more than 2 years, 24.
6 months, and 13.
7 months in the placebo group.
Among patients with tumors expressing PD-L1≥1%, the median NUTRFS of nivolumab and placebo groups were not reached and 10.
9 months, respectively, showing good clinical benefits.
The results of the median NUTRFS analysis showed that adverse reactions were safe and controllable.
The safety of nivolumab is consistent with the safety reported in other solid tumor clinical studies.
The proportions of treatment-related adverse events (TRAEs) in the nivolumab group and placebo group were 77.
5% and 55.
5%, respectively, and the incidence of grade 3 to 4 TRAEs was 17.
9% and 7.
2%, respectively.
"CheckMate-274 is the first and currently the only phase III clinical study that confirmed immunotherapy as an adjuvant treatment for myometrial invasive urothelial carcinoma, and achieved positive results in all random populations and those with PD-L1 expression ≥1%.
"Professor Ye Dingwei explained, "If you let me define, I think this study is the first and currently the only clinical study that proves that immunotherapy is valuable in the adjuvant treatment of bladder cancer, and it has breakthrough significance.
"Across the board, immunotherapy is actively exploring multiple treatment lines for urothelial cancer.
In addition to breakthroughs in the field of adjuvant therapy for urothelial cancer, immunotherapy is also considered to have broad application prospects in multiple treatment lines for bladder cancer.
" This is mainly related to the characteristics of urothelial cancer cells.
Urothelial cancer has strong immunogenicity, its PD-L1 expression level is relatively high, and the tumor mutation burden (TMB) is also high.
Based on the characteristics of these aspects, urothelial cancer is considered to be a “hot tumor”, which is a type of tumor that is relatively “favored” by immunotherapy.
"Professor Ye Dingwei said, "In addition, studies have confirmed that the expression level of PD-L1 is related to the malignancy of urothelial carcinoma, which means that PD-L1 can be used as an indicator of prognosis.
"Higher immunogenicity, higher PD-L1 expression level and higher TMB, the "three highs" characteristics of urothelial cancer have opened up a broad application scenario for the full-line attack of immunotherapy.
At present, more and more Many clinical studies are underway, such as CheckMate-7G8, CheckMate-901, etc.
Immunotherapy represented by nivolumab is expected to bring benefits to patients in many areas of urothelial cancer, including local progression or First-line treatment, second-line treatment, maintenance treatment, adjuvant therapy and perfusion treatment for non-muscular invasive urothelial carcinoma of metastatic urothelial carcinoma.
At the same time, immunotherapy for urothelial carcinoma has also been recognized by many domestic and foreign authoritative clinical guidelines Recommendation: The 2019 European Urology Annual Conference (EAU) Guidelines include immune checkpoint inhibitors in the adjuvant treatment of myometrial infiltrating or metastatic urothelial carcinoma (only applicable to clinical trials) into the guidelines recommendation, and the recommendation level is "strong" "; In the 2019 National Comprehensive Cancer Network (NCCN) Guidelines, PD-1/PD-L1 inhibitors including O drugs are recommended for the treatment of advanced urothelial cancer after platinum-containing chemotherapy.
Line therapy; In 2019, the “Guidelines for the Diagnosis and Treatment of Chinese Urology and Andrology” listed immunotherapy as the recommended treatment for myometrial invasive urothelial carcinoma for the first time. As the domestic leader of the CheckMate-274 study, Professor Ye Dingwei said sincerely at the end of the interview, “I very much look forward to immunotherapy benefiting Chinese patients with genitourinary system tumors as soon as possible and improving their survival and quality of life.
Of course, with the exception of urothelial cancer, Clinical trials of nivolumab in the treatment of kidney cancer and prostate cancer will also be carried out in China, hoping to bring more good news to the clinic.
"Expanded reading In recent years, the exploration of immunotherapy is gradually advancing to the front line, for example, in In the field of adjuvant therapy, immunotherapy has achieved breakthroughs in many tumor types.
Taking nivolumab as an example, it has been confirmed that it has clinically significant efficacy in the adjuvant treatment of four tumor types, including bladder cancer, lung cancer, melanoma, esophageal cancer/gastroesophageal junction cancer.
Front-line exploration of immunotherapy is expected to allow more cancer patients to benefit from survival at an earlier stage and improve the overall prognosis.
