【Explanation】Professor Shen Yijun: 2022 ASCO GU Blockbuster Research First Look

From February 17th to 20th, Eastern Time, the 2022 ASCO GU will come as expected in the expectation of the global urological oncology colleagues
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For Chinese colleagues who are accustomed to tasting this academic feast during the Chinese New Year, this year's ASCO GU is a bit late
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However, a good meal is not afraid of being late.
Let us taste the wonderful academic content of this conference in advance along with the warmth of the Spring Festival
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Expert Profile Professor Shen Yijun is the chief physician of the Department of Urology, Fudan University Affiliated Cancer Hospital, and a postgraduate tutor
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He has been engaged in the diagnosis, treatment and prevention of urogenital tumors for a long time
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Visiting scholar at MD Anderson Cancer Center and University of Texas School of Medicine, member of the Chinese Society of Clinical Oncology (CSCO) Urothelial Cancer Expert Committee, member of the Bladder Cancer Group of the Chinese Anti-Cancer Association Urogenital Oncology Professional Committee, and Urology Department of the Shanghai Medical Association Member of the Physician Branch, expert of the supervision group of the Shanghai Urology Clinical Quality Control Center
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As the project leader, he presided over more than ten projects of the National Natural Science Foundation of China, the Shanghai Natural Science Foundation, and the Shanghai Shenkang Major Clinical Research Project
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The research results are cited in the NCCN Bladder Cancer Guidelines
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【Urothelial carcinoma】Advanced second-line 1、【Oral Abstract Session -Abstract #434】TROPHY-U-01 Cohort 3: Sacituzumab govitecan (SG) in combination with pembrolizumab (Pembro) in patients (pts) with metastatic urothelial cancer (mUC ) who progressed after platinum (PLT)-based regimens.
(NCT03547973) Immunotherapy is the standard of care for patients with advanced UC who have failed platinum-based chemotherapy, but has limited efficacy
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As a star ADC drug targeting Trop-2, SG single-agent has a positive effect in advanced UC patients treated with platinum-based chemotherapy and PD-1 inhibitor, with an ORR of 27%
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TROPHY-U-01 is a Phase II, multi-cohort clinical study
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Cohort 3 enrolled 41 patients with advanced UC who failed platinum-based chemotherapy and received SG combined with K drug treatment.
The median follow-up was 5.
8 months
.

RESULTS: Investigator-assessed ORR was 34% (95% CI, 20.
1-50.
6; 1 CR; 13 PR); CBR was 44% (95% CI, 28.
5-60.
3); 6-month progression-free survival was 47 %
.

Common AEs include diarrhea, nausea, anemia, etc.
; Grade ≥3 TRAEs occurred in 59% of patients
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Late-stage first-line 2.
【Oral Abstract Session-Abstract #437】BAYOU: A phase II, randomized, multicenter, double-blind, study of durvalumab (D) in combination with olaparib (O) for the first-line treatment of platinum-ineligible patients with unresectable, stage IV urothelial carcinoma (UC).
(NCT03459846) Homologous recombination repair gene defects are common in UC, which means that some patients are sensitive to PARP inhibitor therapy
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PARP inhibitors combined with immunotherapy may be more effective
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BAYOU is a randomized, phase II clinical study that included 154 patients with advanced first-line UC who were intolerant to platinum therapy and randomized to receive Durvalumab + olaparib (D+O group, n = 78) and Durvalumab + placebo (D+ Group P, n = 76) treatment, the primary endpoint was median PFS in the IIT population
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The results showed that there was no significant difference in median PFS between the two groups and the primary endpoint was not met
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In the subgroup of HRRm patients, the median PFS was 5.
6 months in the D+O group and 1.
8 months in the D+P group, which was statistically significant
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Grade 3 and 4 AEs occurred in 18% and 9% of the two groups, respectively, and no new safety signals were observed
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3.
【General Session-Abstract #432】First-line pembrolizumab (pembro) with or without lenvatinib (lenva) in patients with advanced urothelial carcinoma (LEAP-011): A phase 3, randomized, double-blind study.
(NCT03898180) LEAP-011 is a randomized, double-blind, global multicenter Phase III study
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Of the 441 patients with locally advanced or metastatic UC who had not received prior systemic therapy, were intolerant to cisplatin, and had positive PD-L1 expression, 218 received pembro + lenva and 223 received pembro + placebo
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The primary endpoints were PFS and OS
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The results showed that the median PFS in the two groups was not statistically significant (pembro + lenva group 4.
2 months vs.
pembro + placebo group 4.
0 months; HR, 0.
91 [95% CI, 0.
71-1.
16]); median OS was also not Statistical significance (pembro + lenva 11.
2 months vs.
pembro + placebo 13.
8 months; HR, 1.
25 [95% CI, 0.
94-1.
67])
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The safety profile of pembro + lenva was consistent with previous studies and no new safety signals were identified
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The failure of this study means that pembro monotherapy remains the standard first-line treatment for platinum-intolerant patients with advanced UC
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4.
【Rapid Abstract Session-Abstract #439】First line avelumab in PD-L1+ve metastatic or locally advanced urothelial cancer (aUC) patients unfit for cisplatin (cis): The ARIES trial.
(NCT03891238) ARIES is a single-arm , An open-label phase II study to explore the efficacy and safety of Avelumab in the first-line treatment of cisplatin-intolerant, PD-L1-positive advanced UC patients.
The primary endpoint is the 1-year OS rate
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As of October 7, 2021, a total of 71 subjects were enrolled, with a median follow-up of 9.
0 months
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The results showed that the median OS was 10.
0 months, and the 1-year OS rate was 40.
8%; the ORR was 22.
5% (1 CR, 15 PR); grade 3 AEs occurred in 5 subjects
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First-line maintenance therapy 5.
【Oral Abstract Session-Abstract #439】A randomized, double blind, biomarker selected, phase II clinical trial of maintenance PARP inhibition following chemotherapy for metastatic urothelial carcinoma (mUC): Final analysis of the ATLANTIS rucaparib arm.
( EudraCT number 2015–003249-25) ATLANTIS study is a multi-controlled phase II clinical study to explore the efficacy of first-line maintenance therapy under different biomarkers and different regimens
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This arm included 74 subjects with unprogressed, biomarker-positive mUC following first-line platinum-based regimens, randomized to rucaparib (n=40) and placebo (n=34), with a primary endpoint of PFS
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RESULTS: mPFS was 35.
3 weeks (80% CI 11.
7-35.
6) in the rucaparib group and 15.
1 weeks (80% CI 11.
9-22.
6) in the placebo group (HR 0.
53, 80% CI 0.
30-0.
92, p = 0.
07); common AEs Fatigue, nausea, and rash, mostly low-grade
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Neoadjuvant therapy and bladder preservation therapy 6.
【Oral Abstract Session-Abstract #435】Study EV-103 Cohort H: Antitumor activity of neoadjuvant treatment with enfortumab vedotin monotherapy in patients (pts) with muscle invasive bladder cancer (MIBC) who are cisplatin -ineligible.
(NCT03288545) Previous Phase II and Phase III clinical trials have confirmed that Enfortumab Vedotin (EV) is safe and effective in the treatment of patients with advanced urothelial carcinoma
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The EV-103 study cohort H aims to explore the efficacy of EV neoadjuvant therapy in cisplatin-intolerant MIBC patients, with the primary endpoint being the pathological complete response rate (pCR)
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A total of 22 patients with cT2-T4aN0M0 MIBC were included.
After 3 cycles of EV therapy, 21 underwent RC+PLND and 1 underwent partial cystectomy
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36.
4% of patients achieved pCR
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The most common TRAEs were fatigue (45.
5%), hair loss (36.
4%) and dysgeusia (36.
4%)
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Grade ≥3 TRAEs occurred in 18.
2% of patients
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None of the subjects experienced surgical delays due to EV treatment
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This cohort demonstrates the promise of EV neoadjuvant therapy in cisplatin-intolerant patients
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7.
【Poster Session-Abstract #499】Real-world study of chemotherapy plus immunotherapy versus chemotherapy alone as neoadjuvant treatment guided bladder-sparing therapy for localized muscle-invasive bladder cancer.
This real-world study is from West China Hospital of Sichuan University, aiming to compare Efficacy of neoadjuvant chemotherapy combined with immunotherapy and chemotherapy alone as one of bladder-sparing therapies for localized MIBC
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A total of 41 MIBC patients with cT2-4bN0-3M0-1a were included in the study, 25 in the combination group and 16 in the chemotherapy group.
The median follow-up time was 15.
3±4.
4 months
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The results showed that the CR rate was 50.
0% in the combination group and 0% in the chemotherapy alone group; the 1-year PFS rates were 95.
5% and 62.
5% in the combination group and chemotherapy group, respectively (p=0.
010), and the 1-year BI-DFS rates were 66.
1% and 66.
1%, respectively.
27.
5% (p=0.
159)
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This study confirms that for locally advanced MIBC, neoadjuvant chemotherapy combined with immunotherapy, as an important bladder-sparing therapy, is more effective than chemotherapy alone, and the toxicity is controllable
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【Renal cell carcinoma】First-line treatment 8.
【General Session-Abstract #288】Phase II study of nivolumab and salvage nivolumab + ipilimumab in treatment-naïve patients (pts) with advanced clear cell renal cell (HCRN GU16-260-Cohort A) : Final report.
(NCT03117309) HCRN GU 16-256 study enrolled 123 ccRCC patients, divided into two phases: patients were first treated with nivo monotherapy (Part A), disease progression within 48 weeks and stable disease at 48 weeks of patients were treated with nivo/ipi for salvage therapy (Part B)
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As of July 4, 2021, with a median follow-up of 26.
9 months, Part A stage ORR (RECIST criteria) was 34.
1% (CR 6.
5%, PR 27.
6%), median DOR was 27.
6 months, and median PFS was 8.
2 month, the 2-year OS rate was 78%
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Sixty-five patients entered Part B, and the ORR for Part B was 11.
4%
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The incidence of grade 3-5 treatment-related adverse reactions in the two treatment periods was 20.
3% and 14.
2%, respectively
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Adjuvant therapy 9.
【Oral Abstract Session-Abstract #290】Pembrolizumab as post nephrectomy adjuvant therapy for patients with renal cell carcinoma: Results from 30-month follow-up of KEYNOTE-564.
(NCT03142334) Keynote 564 is the first renal cell carcinoma Double-blind, multicenter, randomized Phase III study of patients with adjuvant immunotherapy with positive endpoints
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The conference reports the results of the Keynote 564 study at 30.
1 months of follow-up: the DFS benefit of pembrolizumab was maintained (HR 0.
63, 95% CI 0.
50 - 0.
80) and was consistent across subgroups, with a 24-month prognosis.
The estimated DFS rate was 78.
3% vs 67.
3%, with no new grade 3-4 AEs during follow-up
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Neoadjuvant therapy 10.
【Oral Abstract Session-Abstract #289】Efficacy, safety, and biomarker analysis of neoadjuvant avelumab/axitinib in patients (pts) with localized renal cell carcinoma (RCC) who are at high risk of relapse after nephrectomy (NeoAvAx ).
(NCT03341845) Nephron-sparing surgery or radical nephrectomy is the standard treatment for patients with localized renal cancer who can tolerate surgery, but about 10% of patients are at high risk of recurrence, and neoadjuvant therapy can help Downstaging and reducing the risk of recurrence
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Neoavax is a single-arm, phase II study of 40 patients with high-risk non-metastatic clear cell RCC (cT1b-4cN0-1M0, grade 3-4) who received avelumab in combination with axifen for 12 weeks prior to nephrectomy Neoadjuvant tinib therapy, the primary endpoint is the primary tumor (PT) partial response rate (PR, shrinkage ≥ 25%)
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The median PT downstaging rate was 20(0-43.
5)%, and the median significant tumor presence rate after treatment was 50(1-100)%
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During a median follow-up of 23.
5 months, 13 (32%) patients relapsed, with a median time to relapse of 8 months (2-23 months), and 3 died
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Neither median DFS nor OS was currently reached, and treatment did not result in delayed surgery and progression of the original tumor
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【Prostate cancer】mCRPC first-line therapy11、【Oral Abstract Session-Abstract #11】PROpel: Phase III trial of Olaparib and abiraterone versus placebo and abi as first-line therapy for patients with mCRPC.
(NCT03732820) PROpel is a randomized, A double-blind, multi-center, randomized, controlled phase III study, designed to evaluate the efficacy and safety of olaparib combined with abiraterone versus abiraterone single-agent first-line treatment of mCRPC in the entire population, with the primary endpoint being rPFS
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A total of 796 patients were included in the study, with 399 in the experimental group and 397 in the control group
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This interim analysis showed that the study met its primary endpoint: ola + abi treatment significantly prolonged rPFS compared with placebo + abi treatment (24.
8 months vs 16.
6 months; HR 0.
66, 95% CI 0.
54-0.
81, P<0.
000) , and rPFS was statistically different regardless of HRR status
.

OS is currently immature and a trend of OS favoring ola + abi has been observed
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The most common grade ≥3 AE was anemia, which occurred in 15.
1 vs 3.
3% of the ola + abi and placebo + abi groups, respectively
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This result confirms that ola + abi has a significant benefit in the first-line treatment of mCRPC without HRR testing
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12.
【Oral Abstract Session- Abstract #12】Phase 3 MAGNITUDE study: First results of niraparib (NIRA) with abiraterone acetate and prednisone (AAP) as first-line therapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) ) with and without homologous recombination repair (HRR) gene alterations.
(NCT03748641) MAGNITUDE is a randomized, double-blind phase III clinical study evaluating the efficacy of niraparib combined with abiraterone in the treatment of metastatic castration-resistant prostate cancer and safety, the primary endpoint was rPFS
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Subjects were randomly assigned to two study arms according to HRR mutation status, of which 423 HRR BM+ patients were randomized to NIRA + AAP (n = 212) and PBO + AAP (n = 211)
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The conference will announce the results of the study with a median follow-up of 18.
6 months
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As assessed by BICR, compared with the PBO+APP group, the NIRA+APP group significantly improved the rPFS of the BRCA1/2 mutation subgroup and the full HRR BM+ population (16.
6 vs 10.
9 mo and 16.
5 vs 13.
7 mo), decreasing by 47% and 27%, respectively.
% risk of disease progression or death
.

OS data is not yet mature
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No new safety signals emerged, with grade 3/4 AEs in 67% and 46.
4% of the NIRA + AAP and PBO + AAP groups, respectively, in HRR BM+ patients
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There were no clinically significant differences in overall quality of life (FACT-P)
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Reference: https://conferences.
asco.
org/gu/attend?cmpid=cc_ascoorg_gu_register_psrh_googleadwords_brand_011322_021622___ta1&gclid=Cj0KCQiA_8OPBhDtARIsAKQu0gZUrdmX-WXL_Y2-G9LrJ_Lz-o5jV2q49Fdi28UBcAshOElKjrv