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Introduction In recent years, the exploration of immunotherapy is making great strides forward
.
At present, immunotherapy has made great progress in the field of neoadjuvant and adjuvant therapy for urothelial carcinoma (UC) and renal cell carcinoma (RCC), which is expected to allow more patients to benefit from the early stage of the disease, thereby improving the long-term survival prognosis
.
Recently, the 2021 European Society of Medical Oncology Annual Conference (ESMO 2021) was successfully held.
Due to the impact of the new crown epidemic, domestic oncologists could not come to the site to participate in the event.
BeiGene specially held the "Jiyu·Hundreds-2021 ESMO GU Highlight" "Online conference, inviting domestic colleagues to share cutting-edge progress in the field of urinary oncology
.
In this meeting, Professor Bao Yige from West China Hospital of Sichuan University gave a detailed interpretation of the progress of UC/RCC perioperative immunotherapy
.
Yimaitong organized the key contents as follows for readers .
Expert Profile Professor Bao Yige, Associate Professor of Urology, West China Hospital, Sichuan University, Doctor of Medicine, Sichuan University, Doctor of Science, University of Western Ontario, Canada, Deputy Chairman of Urology Branch of Sichuan Medical Association, Youth Committee of Urology Branch of China Anticancer Association, Chinese Research Hospital Association Urology Young member of the Surgery Professional Committee Young member of the Sichuan Provincial Reproductive Medicine Professional Committee Member of the Robot and Artificial Intelligence Physician Branch of the Sichuan Medical Association Member UC/RCC Adjuvant Immunotherapy: Moving Forward in Controversy, Professor Bao Yige pointed out that in 2021, UC and RCC Two major adjuvant immunotherapy studies in the field-CheckMate-274 and KEYNOTE-564 studies announced positive results, demonstrating the value of adjuvant immunotherapy
.
Prior to these two studies, adjuvant therapy has been in chaos and contradictions for a long time, whether it is in the field of UC or RCC
.
1CheckMate-274 study: Significance and controversy of UC adjuvant immunotherapy The CheckMate-274 study is a randomized, double-blind, multi-center, phase III clinical trial designed to evaluate nivolumab versus placebo after radical surgery Efficacy and safety of patients with muscular invasive bladder cancer (MIBC) at high risk of recurrence
.
The population included in the study includes two major categories, one is patients who have received neoadjuvant therapy and the pathology is still MIBC after surgery, and the other is patients who have not received neoadjuvant therapy and have pT3-T4 or lymph node positive after surgery.
These patients are randomized to receive Up to one year of adjuvant therapy with nivolumab or placebo
.
At present, the overall survival (OS) results of the study have not been reached, the primary endpoint of disease-free survival (DFS) is a positive result, and the survival benefit of PD-L1 positive patients seems to be more significant
.
Professor Bao Yige said that in the past, MIBC adjuvant treatment data were only based on retrospective studies, and the results of different retrospective studies often conflicted with each other
.
The results of the CheckMate-274 study confirm that adjuvant immunotherapy is feasible, which brings a turning point for adjuvant immunotherapy, but there is also some controversy in this research
.
First, from the disease-free survival (DFS) curve, the gap between the two groups at the initial stage is large, and gradually approaches in the later stage
.
Second, whether the OS will benefit in the end is an unresolved question in CheckMate-274 research
.
For UC patients, should they choose first-line immunotherapy or adjuvant immunotherapy? Professor Bao said that although patients receive first-line treatment after adjuvant therapy relapses, the two types of patients are in completely different disease states
.
During adjuvant treatment, the patient's primary tumor has just been removed and the tumor burden is very small, but most patients do not have the primary tumor and the tumor burden is heavier during the first-line treatment
.
Based on historical research and adjuvant therapy purposes, Professor Bao explored this issue from three perspectives: First, from the perspective of prolonging survival, the EORTC 30994 study showed that the PFS benefit of immediate postoperative adjuvant chemotherapy is better than delayed Adjuvant chemotherapy, although the results of this study cannot be directly derived into immunotherapy, it also provides a good direction for clinical follow-up research
.
Secondly, from the perspective of cure rate, the current research data is limited
.
In the CheckMate-274 study, 35% of the patients in the control group did not relapse without receiving any adjuvant therapy.
It can be seen that adjuvant immunotherapy requires population screening to avoid overtreatment
.
Finally, from the perspective of delaying recurrence, patients who did not receive cisplatin chemotherapy in the CheckMate-274 study had a median DFS benefit of 10 months for adjuvant immunotherapy; while the median OS of patients in the KEYNOTE-052 study was 11.
3 months.
, Suggesting that the benefit of adjuvant immunotherapy DFS has certain value for these patients
.
However, it is worth noting that the results of the CheckMate-274 study are not directly equivalent to the efficacy of patients who are intolerant to cisplatin, because the study actually enrolled some patients who could tolerate cisplatin but refused to receive cisplatin treatment.
This part of the population The results of immunotherapy may be better than those of people who cannot tolerate chemotherapy
.
Professor Bao Yige pointed out that in the age of immunotherapy, the screening of adjuvant therapy patients is a clinical issue of greatest concern
.
Comprehensive analysis of the results of CheckMate-274 and IMvigor 010, we can find that: on the one hand, disease classification and staging will affect the efficacy of adjuvant immunotherapy; on the other hand, ctDNA-positive patients receiving adjuvant immunotherapy seem to have better results
.
In addition, with the increase in the types of drugs and the number of treatment lines, how to choose the indicators for evaluating the efficacy of the back line still needs to be further explored
.
2KEYNOTE-564 Study: Gains and Thoughts on RCC Adjuvant Immunotherapy The KEYNOTE-564 study is a randomized, double-blind, phase Ⅲ clinical trial designed to evaluate the high-risk and high-risk of pembrolizumab as a single-agent adjuvant therapy after nephrectomy Or M1 no evidence of disease (M1 NED) the efficacy and safety of RCC patients
.
The results showed that compared with placebo, patients treated with pembrolizumab had a statistically significant and clinically significant improvement in the primary endpoint of DFS, and the OS data is not yet mature
.
Professor Bao Yige said that in the field of RCC adjuvant therapy, in the past few years, except for the STRAC study, all adjuvant targeted therapy studies have had negative results
.
The KEYNOTE-564 study is the first immunotherapy study in the field of RCC to reach the primary research endpoint, and its positive results are encouraging
.
At the same time, the study also has many questions to be answered.
The most worthy of investigation is that KEYNOTE-564, as an adjuvant immunotherapy study, enrolled 5.
8% of M1 NED patients.
The overall treatment benefit of this part of patients is better than M0.
The patient has a certain impact on the final result
.
For RCC patients, the choice of first-line immunotherapy or adjuvant immunotherapy is also of concern
.
Professor Bao Yige shared that although there is no direct comparison, in the KEYNOTE-426 and CheckMate-214 studies, 30% to 37% of patients received first-line combination therapy and the long-term disease-free results are exciting; KEYNOTE-564 In the study, the DFS curve splits at 3 months after surgery and seems to be able to benefit early.
These data suggest the significance of adjuvant immunotherapy in delaying the recurrence of the disease
.
Professor Bao Yige also pointed out that adjuvant immunotherapy needs to consider safety issues, especially endocrine toxicity
.
Therefore, when performing immunotherapy, it is necessary to balance risks and benefits
.
In addition, patient selection is a common problem faced by clinical practice of adjuvant immunotherapy
.
Preoperative neoadjuvant therapy for UC/RCC: New era 1 MIBC hotspots and development: treatment based on the efficacy of neoadjuvant therapy.
In the field of MIBC, the efficacy of neoadjuvant therapy is very accurate, whether it is neoadjuvant chemotherapy or neoadjuvant immune monotherapy , Or neoadjuvant chemotherapy combined with immunotherapy studies have achieved positive results
.
At present, a more flexible variant of neoadjuvant therapy is to combine neoadjuvant therapy with bladder preservation, that is, according to the curative effect of neoadjuvant therapy, choose to cut the bladder or preserve the bladder
.
The HCRN GU 16-257 and RETAIN-2 studies are both explorations of this variant.
This more flexible and comprehensive treatment may be the future direction of MIBC, which can provide patients with more options
.
2 The future road of RCC: Combination therapy or the way forward.
In the field of RCC, the research data of neoadjuvant therapy is relatively small.
Among them, the efficacy of neoadjuvant targeted therapy is limited, and the efficacy of immune single agent is not satisfactory
.
In the era of target immunity and double immunity, combined therapy has brought a glimmer of hope, or a new world worth exploring in the future
.
In summary, in the field of UC and RCC adjuvant immunotherapy, the CheckMate-274 study and the KEYNOTE-564 study have achieved new breakthroughs.
“Immunotherapy in the first-line or in the adjuvant phase” is a hot topic of controversy
.
The choice of adjuvant therapy needs to weigh the survival benefits and side effects of drug therapy
.
Therefore, determining the patients most likely to benefit from adjuvant therapy is the primary consideration in the implementation of adjuvant therapy
.
In the field of neoadjuvant immunotherapy, the strategy of stratifying treatment based on the efficacy of neoadjuvant is the development direction of MIBC.
Although the exploration of neoadjuvant immunotherapy in RCC is at an early stage, it will be in the future for tumor reduction surgery and tumor thrombus reduction.
Both period and kidney-sparing surgery can play an important role
.
To watch the conference replay video, click "Read the original text" below
.
At present, immunotherapy has made great progress in the field of neoadjuvant and adjuvant therapy for urothelial carcinoma (UC) and renal cell carcinoma (RCC), which is expected to allow more patients to benefit from the early stage of the disease, thereby improving the long-term survival prognosis
.
Recently, the 2021 European Society of Medical Oncology Annual Conference (ESMO 2021) was successfully held.
Due to the impact of the new crown epidemic, domestic oncologists could not come to the site to participate in the event.
BeiGene specially held the "Jiyu·Hundreds-2021 ESMO GU Highlight" "Online conference, inviting domestic colleagues to share cutting-edge progress in the field of urinary oncology
.
In this meeting, Professor Bao Yige from West China Hospital of Sichuan University gave a detailed interpretation of the progress of UC/RCC perioperative immunotherapy
.
Yimaitong organized the key contents as follows for readers .
Expert Profile Professor Bao Yige, Associate Professor of Urology, West China Hospital, Sichuan University, Doctor of Medicine, Sichuan University, Doctor of Science, University of Western Ontario, Canada, Deputy Chairman of Urology Branch of Sichuan Medical Association, Youth Committee of Urology Branch of China Anticancer Association, Chinese Research Hospital Association Urology Young member of the Surgery Professional Committee Young member of the Sichuan Provincial Reproductive Medicine Professional Committee Member of the Robot and Artificial Intelligence Physician Branch of the Sichuan Medical Association Member UC/RCC Adjuvant Immunotherapy: Moving Forward in Controversy, Professor Bao Yige pointed out that in 2021, UC and RCC Two major adjuvant immunotherapy studies in the field-CheckMate-274 and KEYNOTE-564 studies announced positive results, demonstrating the value of adjuvant immunotherapy
.
Prior to these two studies, adjuvant therapy has been in chaos and contradictions for a long time, whether it is in the field of UC or RCC
.
1CheckMate-274 study: Significance and controversy of UC adjuvant immunotherapy The CheckMate-274 study is a randomized, double-blind, multi-center, phase III clinical trial designed to evaluate nivolumab versus placebo after radical surgery Efficacy and safety of patients with muscular invasive bladder cancer (MIBC) at high risk of recurrence
.
The population included in the study includes two major categories, one is patients who have received neoadjuvant therapy and the pathology is still MIBC after surgery, and the other is patients who have not received neoadjuvant therapy and have pT3-T4 or lymph node positive after surgery.
These patients are randomized to receive Up to one year of adjuvant therapy with nivolumab or placebo
.
At present, the overall survival (OS) results of the study have not been reached, the primary endpoint of disease-free survival (DFS) is a positive result, and the survival benefit of PD-L1 positive patients seems to be more significant
.
Professor Bao Yige said that in the past, MIBC adjuvant treatment data were only based on retrospective studies, and the results of different retrospective studies often conflicted with each other
.
The results of the CheckMate-274 study confirm that adjuvant immunotherapy is feasible, which brings a turning point for adjuvant immunotherapy, but there is also some controversy in this research
.
First, from the disease-free survival (DFS) curve, the gap between the two groups at the initial stage is large, and gradually approaches in the later stage
.
Second, whether the OS will benefit in the end is an unresolved question in CheckMate-274 research
.
For UC patients, should they choose first-line immunotherapy or adjuvant immunotherapy? Professor Bao said that although patients receive first-line treatment after adjuvant therapy relapses, the two types of patients are in completely different disease states
.
During adjuvant treatment, the patient's primary tumor has just been removed and the tumor burden is very small, but most patients do not have the primary tumor and the tumor burden is heavier during the first-line treatment
.
Based on historical research and adjuvant therapy purposes, Professor Bao explored this issue from three perspectives: First, from the perspective of prolonging survival, the EORTC 30994 study showed that the PFS benefit of immediate postoperative adjuvant chemotherapy is better than delayed Adjuvant chemotherapy, although the results of this study cannot be directly derived into immunotherapy, it also provides a good direction for clinical follow-up research
.
Secondly, from the perspective of cure rate, the current research data is limited
.
In the CheckMate-274 study, 35% of the patients in the control group did not relapse without receiving any adjuvant therapy.
It can be seen that adjuvant immunotherapy requires population screening to avoid overtreatment
.
Finally, from the perspective of delaying recurrence, patients who did not receive cisplatin chemotherapy in the CheckMate-274 study had a median DFS benefit of 10 months for adjuvant immunotherapy; while the median OS of patients in the KEYNOTE-052 study was 11.
3 months.
, Suggesting that the benefit of adjuvant immunotherapy DFS has certain value for these patients
.
However, it is worth noting that the results of the CheckMate-274 study are not directly equivalent to the efficacy of patients who are intolerant to cisplatin, because the study actually enrolled some patients who could tolerate cisplatin but refused to receive cisplatin treatment.
This part of the population The results of immunotherapy may be better than those of people who cannot tolerate chemotherapy
.
Professor Bao Yige pointed out that in the age of immunotherapy, the screening of adjuvant therapy patients is a clinical issue of greatest concern
.
Comprehensive analysis of the results of CheckMate-274 and IMvigor 010, we can find that: on the one hand, disease classification and staging will affect the efficacy of adjuvant immunotherapy; on the other hand, ctDNA-positive patients receiving adjuvant immunotherapy seem to have better results
.
In addition, with the increase in the types of drugs and the number of treatment lines, how to choose the indicators for evaluating the efficacy of the back line still needs to be further explored
.
2KEYNOTE-564 Study: Gains and Thoughts on RCC Adjuvant Immunotherapy The KEYNOTE-564 study is a randomized, double-blind, phase Ⅲ clinical trial designed to evaluate the high-risk and high-risk of pembrolizumab as a single-agent adjuvant therapy after nephrectomy Or M1 no evidence of disease (M1 NED) the efficacy and safety of RCC patients
.
The results showed that compared with placebo, patients treated with pembrolizumab had a statistically significant and clinically significant improvement in the primary endpoint of DFS, and the OS data is not yet mature
.
Professor Bao Yige said that in the field of RCC adjuvant therapy, in the past few years, except for the STRAC study, all adjuvant targeted therapy studies have had negative results
.
The KEYNOTE-564 study is the first immunotherapy study in the field of RCC to reach the primary research endpoint, and its positive results are encouraging
.
At the same time, the study also has many questions to be answered.
The most worthy of investigation is that KEYNOTE-564, as an adjuvant immunotherapy study, enrolled 5.
8% of M1 NED patients.
The overall treatment benefit of this part of patients is better than M0.
The patient has a certain impact on the final result
.
For RCC patients, the choice of first-line immunotherapy or adjuvant immunotherapy is also of concern
.
Professor Bao Yige shared that although there is no direct comparison, in the KEYNOTE-426 and CheckMate-214 studies, 30% to 37% of patients received first-line combination therapy and the long-term disease-free results are exciting; KEYNOTE-564 In the study, the DFS curve splits at 3 months after surgery and seems to be able to benefit early.
These data suggest the significance of adjuvant immunotherapy in delaying the recurrence of the disease
.
Professor Bao Yige also pointed out that adjuvant immunotherapy needs to consider safety issues, especially endocrine toxicity
.
Therefore, when performing immunotherapy, it is necessary to balance risks and benefits
.
In addition, patient selection is a common problem faced by clinical practice of adjuvant immunotherapy
.
Preoperative neoadjuvant therapy for UC/RCC: New era 1 MIBC hotspots and development: treatment based on the efficacy of neoadjuvant therapy.
In the field of MIBC, the efficacy of neoadjuvant therapy is very accurate, whether it is neoadjuvant chemotherapy or neoadjuvant immune monotherapy , Or neoadjuvant chemotherapy combined with immunotherapy studies have achieved positive results
.
At present, a more flexible variant of neoadjuvant therapy is to combine neoadjuvant therapy with bladder preservation, that is, according to the curative effect of neoadjuvant therapy, choose to cut the bladder or preserve the bladder
.
The HCRN GU 16-257 and RETAIN-2 studies are both explorations of this variant.
This more flexible and comprehensive treatment may be the future direction of MIBC, which can provide patients with more options
.
2 The future road of RCC: Combination therapy or the way forward.
In the field of RCC, the research data of neoadjuvant therapy is relatively small.
Among them, the efficacy of neoadjuvant targeted therapy is limited, and the efficacy of immune single agent is not satisfactory
.
In the era of target immunity and double immunity, combined therapy has brought a glimmer of hope, or a new world worth exploring in the future
.
In summary, in the field of UC and RCC adjuvant immunotherapy, the CheckMate-274 study and the KEYNOTE-564 study have achieved new breakthroughs.
“Immunotherapy in the first-line or in the adjuvant phase” is a hot topic of controversy
.
The choice of adjuvant therapy needs to weigh the survival benefits and side effects of drug therapy
.
Therefore, determining the patients most likely to benefit from adjuvant therapy is the primary consideration in the implementation of adjuvant therapy
.
In the field of neoadjuvant immunotherapy, the strategy of stratifying treatment based on the efficacy of neoadjuvant is the development direction of MIBC.
Although the exploration of neoadjuvant immunotherapy in RCC is at an early stage, it will be in the future for tumor reduction surgery and tumor thrombus reduction.
Both period and kidney-sparing surgery can play an important role
.
To watch the conference replay video, click "Read the original text" below
