A hundred flowers bloom!

*Only for medical professionals to read for reference, Fudan Cancer Masters Interpretation of 2021 ASCO Urinary Tumor Diagnosis and Treatment New Progress! The 2021 American Society of Clinical Oncology (ASCO) annual meeting will be held online from June 4th to 8th.
As one of the largest and most popular events in the oncology field, it will show scholars from all walks of life the latest cutting-edge progress in the field of oncology every year
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"Experts on complex tumors will take you to the 2021 ASCO-Urinary Oncology Special".
Professor Zhu Yao, Professor Zhang Hailiang, Professor Shen Yijun and Professor Su Hengchuan from Fudan University Affiliated Tumor Hospital will be invited to discuss prostate cancer, kidney cancer, urothelial cancer and reproductive tumors.
A wonderful interpretation of the blockbuster research in the direction of several colleges and universities, conveying cutting-edge trends
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 Professor Zhu Yao: Interpretation of important clinical researches on prostate cancer VISION, PEACE-1, SWOGS1216, 177Lu-PSMA-617 in the Phase III study of metastatic castration-resistant prostate cancer (abstract number: LBA4 study name VISION) in this study All patients must have received new endocrine therapy and one or two copeptins chemotherapy (docetaxel or cabazitaxel)
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In addition, all patients must have prostate-specific antigen (PSMA)-positive lesions
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In this study, standard treatment (SOC) strictly excluded chemotherapy, immunotherapy, and radium-223 treatments
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One group was treated with SOC+177Lu-PSMA-617, every 6 weeks, a total of 4 cycles, if there is residual, it was extended to 6 cycles, and the other group was treated with SOC alone
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Figure 1: VISION's study design The study found that 177Lu-PSMA-617 prolonged the overall survival (OS) of patients, the overall risk of death was reduced by 38%, and the median survival time reached 15.
3 months without the use of 177Lu-PSMA- The median survival time of 617 patients was 11.
3 months
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From the imaging point of view, the risk of progression of patients in the 177Lu-PSMA-617 group was reduced by 60%, and the progression time was extended from 3.
4 months to 8.
7 months; from the perspective of PSA reduction, more than half of the patients in the 177Lu-PSMA-617 group The reduction of PSA in patients is ≥50%, while the reduction of PSA in the SOC group is relatively small; from the point of view of safety, the side effects of 177Lu-PSMA-617 are relatively large, mainly reflected in fatigue (49.
1%) and bone marrow suppression (47.
4%) , Dry mouth (39.
3%) and nausea and vomiting (39.
3)
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For clinical studies of patients with metastatic castration-resistant prostate cancer, including VISION, it can basically prolong OS to 3 to 4 months.
It can be seen that OS is still relatively limited, and clinical intervention can be considered as soon as possible
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177Lu-PSMA-617 has a good prospect in the treatment of metastatic castration-resistant prostate cancer (mCRPC), but the side effects of the drug still need to be considered
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Figure 2: For patients with mCRPC, based on previous studies, overall prolonging the overall survival time of patients by 3 to 4 months 2.
The effect of chemotherapy + abiraterone + local radiotherapy in newly diagnosed metastatic hormone-sensitive prostate cancer (Abstract number: 5000, study name PEACE-1) The study included a total of 1173 patients with metastatic hormone-sensitive prostate cancer (mCSPC).
The SOC was androgen deprivation therapy (ADT) + docetaxel.
They were divided into several treatment groups, namely SOC (n=296), SOC+abiraterone (n=292), SOC+radiotherapy (n=293), SOC+abiraterone+radiotherapy (n=292), the specific plan can be seen in Figure 3
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Figure 3: The research results of the specific schemes of the standard treatment group and the experimental treatment group show that compared with the SOC group, the SOC+abiraterone and SOC+abiraterone+radiotherapy groups reduce the risk of progression by 46%, and the time for progression is extended by nearly 2.
3 years.
This data is encouraging
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But from the point of view of side effects, the side effects of this triple scheme are relatively serious, including high blood pressure and neutrophil deficiency
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In addition, another study (SWOGS1216) explored the efficacy of ADT+Orteronel and ADT+bicalutamide in patients with mCSPC
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The study found that although the overall survival of patients in the ADT+Orteronel group was prolonged, it did not meet the preset standard.
The time of progression of this group of patients was also extended to 47.
6 months, and the risk of progression was reduced to 42%
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Figure 4: Toxicity of drugs in the standard treatment group and the experimental group (grades 3-5).
From the two studies of PEACE-1 and SWOGS1216, it can be found that although the time to progression of the imaging manifestations of the experimental group patients has been better prolonged, but The OS does not extend significantly
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Therefore, for drug-resistant patients, the clinic should evaluate the patients according to the risk gradient, and then give the corresponding treatment, instead of all patients using the same treatment
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Professor Zhang Hailiang: Interpretation of important clinical trials for kidney cancer Keynote564, Poster4550 1.
A randomized, double-blind, placebo-controlled, phase III clinical trial to evaluate the efficacy and safety of pembrolizumab as an adjuvant therapy for renal cell carcinoma (Abstract number: LBA5, study name KEYNOTE-564) The key inclusion criteria are medium to high risk (T2 G4, T3), high risk (T4, T) or M1 NED renal clear cell carcinoma, advanced disease that has not previously received systemic treatment, complete or partial nephrectomy (M1 underwent resection of metastases NED) surgical margin negative and disease-free survival, eastern cooperative Oncology group (ECOG) performance status 0/1 and so on
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Patients in the experimental group received 200 mg of pembrolizumab intravenously, once every 3 weeks
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Pembrolizumab adjuvant therapy for patients with intermediate, high-risk, or metastatic resection of renal cancer has higher 1-year and 2-year disease-free survival (DFS) rates than placebo
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1-year DFS rate: 85.
7% vs 76.
2%; 2-year DFS rate: 77.
3% vs 68.
1%
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Figure 5: DFS comparison between pembrolizumab group and placebo group, but the problems still cannot be ignored.
Pembrolizumab single drug is not approved for the treatment of advanced renal cancer; the control group is a placebo.
Rather than sunitinib; all patients were enrolled in clear cell renal cell carcinoma; the baseline PD-L1 positive expression rate was as high as 70%
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Sunitinib is an effective drug in the past.
If it is used as a control group, then the effect of pembrolizumab treatment will have a better control
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Included are patients with renal clear cell carcinoma.
Whether pembrolizumab is effective in patients with non-renal clear cell carcinoma is unknown
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In this study, the baseline PD-L1 positive expression rate was as high as 70%, and patients with negative PD-L1 expression would not necessarily benefit from the use of pembrolizumab
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2.
An open, non-randomized, multi-center, phase II clinical trial of carrelizumab combined with famitinib malate in the treatment of advanced renal cell carcinoma (abstract number: Poster 4550, study name NCT03827837) This study is a double-arm study At the same time, two cohorts of renal clear cell carcinoma and urothelial carcinoma were included.
The treatment plan was famitinib 20 mg once a day, oral + carrelizumab 200 mg once every three weeks, and intravenous injection
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And we mainly focus on the cohort of renal clear cell carcinoma
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The study found that carrelizumab combined with famitinib malate showed good anti-tumor activity in advanced RCC without adding a new safety burden
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The objective response rate (ORR) reached 60.
5%; the disease control rate (DCR) reached 89.
5%; the median progression-free survival (PFS) reached 18.
8 months; the 12-month OS rate reached 88.
0%
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It is worth noting that in patients with renal cell carcinoma who have received multiple lines of treatment in the past, considerable ORR has been observed
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Among the 25 treated patients, 15 received first-line systemic treatment, 6 received second-line treatment, and 4 received more than second-line treatment
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The ORR between the carrelizumab combined with famitinib malate treatment group and the untreated group was 48.
0% and 84.
6%, respectively
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Figure 6: Median PFS and OS in the renal cell carcinoma cohort Professor Shen Yijun: First-line pembrolizumab in patients with advanced urothelial carcinoma who are intolerant to cisplatin KEYNOTE-052 Phase II clinical study KEYNOTE-052 enrolled 370 A patient with advanced urothelial cancer, these patients are intolerant to cisplatin
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The researchers administered 200 mg of pembrolizumab intravenously every 3 weeks to the enrolled patients, and evaluated them by CT/MRI every 9 weeks after the first dose, every 6 weeks for a year, and every 12 weeks after a year.
Curative effect
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The results of the study show that pembrolizumab alone can be used for the treatment of advanced urothelial cancer intolerant to cisplatin
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From the 5-year follow-up results, the median survival time of patients was 11.
3 months, especially for patients with high PD-L1 expression, that is, CPS score ≥10 points, the median survival time reached 18.
5 months
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The patient's ORR is close to 30%, especially for patients with a CPS score ≥10, the ORR reaches 47.
3%
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Compared with traditional treatment methods, this ORR is not low, and the ORR of traditional treatment is about 20%
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In terms of drug safety, less than 10% of patients discontinued treatment due to drug side effects, and immune adverse reactions above grade 3 are relatively rare (below 2.
4%).
From these data, the drug is still quite safe
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Figure 7: 5-year survival of patients enrolled in the KEYNOTE-052 study Figure 8: Evaluation of the safety of pembrolizumab.
Chemotherapy is still the cornerstone of the treatment of advanced urothelial cancer
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Platinum-based chemotherapy is still the basis for the treatment of advanced urothelial cancer, because whether it is the gemcitabine + cisplatin regimen or the methotrexate + vinblastine + doxorubicin + cisplatin (ddMVAC) regimen, the median survival time can reach 14-15 months
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In the IMvigor-130 and KEYNOTE-361 studies, atelizumab + chemotherapy, placebo + chemotherapy, pembrolizumab + chemotherapy, these immune combination chemotherapy regimens did not improve the OS of patients with advanced urothelial cancer And PFS
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However, in the KEYNOTE-361 study, from the ORR point of view, the gemcitabine + carboplatin regimen was higher than the regimen of pembrolizumab alone (including PD-L1 high expression population), but the OS of these two regimens was not significant Difference
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Figure 9: IMvigor-130 and KEYNOTE-361 studies show that there is no positive result of OS in combination with immunotherapy Professor Su Hengchuan: Interpretation of male reproductive system tumor research (Abstract No.
5007, 5018, 5027) 1.
FDG PET-CT in Phase I and Clinical application in advanced testicular seminoma (abstract number: 5007) Testicular cancer is the most common reproductive system tumor in western men.
FDG PET-CT is a method to evaluate the residual lesions of testicular seminoma after chemotherapy, but FDG The use of PET-CT is not very clear
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This study mainly explores the value of FDG PET-CT in evaluating the positive predictive rate (PPV) and negative predictive rate (NPV) of testicular seminoma
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The study found that among 181 patients with stage I seminoma, the PPV of conventional FDG PET-CT reached 100% and the NPV reached 97%
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For some suspicious lesions, the PPV of FDG PET-CT is still 100%, and the NPV is 91%; for 77 patients with advanced seminoma, the PPV of conventional FDG PET-CT is still 69%, and the NPV is 100%; For suspicious lesions, the PPV of FDG PET-CT is still 88%, and the NPV is 94%
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It can be seen that FDG PET-CT has high PPV and NPV for suspicious lesions regardless of stage I or advanced stage patients
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FDG PET-CT can be used to predict the risk of recurrence in seminoma
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Figure 10: Prediction results of FDG PET-CT in stage I seminoma 2.
Monitoring of complete remission in patients with non-seminoma after chemotherapy (Abstract No.
5018) This study has achieved complete remission after first-line chemotherapy ( CR) non-seminoma patients were followed up for observation
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The results of the study showed that with a median follow-up of 3.
4 years, 93.
6% of patients were tumor-free and 2.
6% were dead; the 2-year PFS was 90.
1%, and the 2-year OS rate was 97.
8%
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There were 34 cases (9%) of patients progressing, of which 16 cases only occurred in retroperitoneum, 3 cases of teratoma were malignant, 11 cases were treated with surgery, 12 cases were salvage chemotherapy, and 11 cases were combined with surgery and chemotherapy
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The study found that 21 patients are still tumor-free, 10 died, and 3 were lost to follow-up
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Patients with non-seminoma who reach CR after first-line chemotherapy can be observed, and if the recurrence can be controlled by surgery or chemotherapy
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Figure 11: Follow-up results of 388 non-seminoma patients III.
Late recurrence of germ cell tumors: detection and treatment results (Abstract No.
5027) This study enrolled 2712 patients with germ cell tumors for follow-up, greater than 2 Years of recurrence is called late recurrence
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Unlike other tumors, germ cell tumors still have a certain recurrence after more than 2 years, so they need to be monitored for late recurrence
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Patients with germ cell tumors require long-term follow-up.
Alpha-fetoprotein (AFP), chorionic gonadotropin (HCG), chest CT and abdominal CT are routine methods for monitoring recurrence
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Ninety-seven patients (3%) experienced late recurrence.
The average age of these patients was 35 years.
The primary lesion was in the testis in 98%, followed by retroperitoneum in 1%, and the mediastinum in 1%
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Among these relapsed patients, 62% of patients who had received chemotherapy were positive for AFP, and 50% of patients who had not received chemotherapy had positive imaging results
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In the recurrence of the lesions, retroperitoneum accounted for the majority, more than 50%, followed by lung and liver
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For relapsed patients, surgery is still the first choice for treatment
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Among the 97 relapsed patients, whether they were previously received chemotherapy or no chemotherapy, among the three treatments of surgery, chemotherapy, and surgery + chemotherapy, the 2-year PFS of patients treated with surgery alone was the highest
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