Explore the frontiers of urology in 2021 ESMO new progress

Editor's note The 2021 European Society of Medical Oncology (ESMO) will be held from September 16th to 21st, and it has come to a perfect end
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As an annual event in the oncology field, in order to enable the majority of urological oncologists to understand the new developments of ESMO, the editor specially selects the following abstracts for readers
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LBA25ARCHES study final OS analysis: a phase III, randomized, double-blind, placebo-controlled study of enzalutamide + ADT in the treatment of mHSPC 01 Research background ARCHES study (NCT02677896) aims to compare enzalutamide + androgen deprivation The efficacy of treatment (ADT) or placebo + ADT for patients with metastatic hormone-sensitive prostate cancer (mHSPC).
Past results have shown that compared with the placebo group, the enzalutamide group significantly reduces the risk of imaging progression in mHSPC patients.
Improved the secondary ending
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Overall survival (OS) is a key secondary endpoint of ARCHES and a key benchmark for clinical efficacy, which was not yet mature at the time of the first analysis
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The ESMO conference reported the final OS (after 356 events)
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02 Research methods The study included 1150 patients with new or relapsed mHSPC, and they were randomly assigned to the enzalutamide group or placebo group at 1:1, stratified according to disease burden and whether they received docetaxel in the past
.

At the time of data cutoff and unblinding, 180 (31.
3%) patients in the placebo group were crossed over to the enzalutamide group
.

Based on the O'Brien-Fleming boundary, the study performed a stratified log-rank test in OS with a two-sided significance level of 0.
04
.

The time of OS Kaplan-Meier and follow-up anti-tumor treatment (TTNAnti) was reported, and the hazard ratios (HRs) were estimated based on the stratified Cox proportional hazard model
.

Figure 1 ARCHES Study Design 03 Study Results As of May 28, 2021, 397 (34.
5%) patients are still receiving treatment, with a median follow-up time of 44.
6 months
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The median treatment time for the enzalutamide group was 40.
2 months, the median treatment time for the placebo group was 13.
8 months, and the median treatment time for crossover patients was 23.
9 months
.

The results showed that compared with the placebo group, the enzalutamide group significantly prolonged OS (HR=0.
66; 95% CI: 0.
53-0.
81; p<0.
0001), and the results were similar in most pre-specified subgroups
.

After 48 months of follow-up, the OS rate of the enzalutamide group was 71%, which was much higher than that of the placebo group (57%)
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Figure 2 The final OS results of the ARCHES trial At the same time, the study showed that compared with the placebo group, the enzalutamide group significantly prolonged TTNAnti, and the safety results were consistent with the preliminary analysis results
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04 Research conclusions This analysis finally showed that enzalutamide + ADT can significantly prolong the survival of patients, and is safe tolerated, and has significant clinical benefits for mHSPC patients
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LBA26Dalotamide maintenance therapy for mCRPC in non-progressive disease after previous NHA treatment and sequential treatment with taxanes: a randomized, double-blind, placebo-controlled phase II trial (SAKK 08/16) 01 Research background With the development of new endocrine therapy (NHA), the diagnosis and treatment team for metastatic castration-resistant prostate cancer (mCRPC) continues to expand
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The researchers hypothesized that after receiving NHA treatment, patients who have achieved stable disease through chemotherapy, receiving dalotamide for maintenance therapy can delay disease progression
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02 Research method SAKK 08/16 study included mCRPC patients who had previously received NHA treatment and had no disease progression after treatment with taxanes (docetaxel ≥300mg/m2 or cabazitaxel ≥80mg/m2)
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Patients started to receive dalotamide 600 mg bd or placebo 2-8 weeks after the end of taxane treatment
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The primary endpoint is the 12-week imaging progression-free survival rate (rPFS12), and the secondary endpoints include imaging progression-free survival (rPFS), event-free survival (EFS), OS, PSA50 remission rate (PSA50 RR), and adverse events ( AE)
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03 Research results From March 2017 to November 2020, a total of 92 patients were enrolled
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The median follow-up time was 18 months, and the median age was 72 years (55-87 years)
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Compared with the placebo group, rPFS12 in the dalotamide group was significantly increased (64.
7% vs 52.
2%, P=0.
127, which was lower than the significant level of 0.
15)
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The median rPFS of the dalotamide group and the placebo group were 5.
5 months and 4.
5 months, respectively (HR=0.
54; 95%CI: 0.
32-0.
91; P=0.
017); median EFS were 5.
4 months and 2.
9 months, respectively Months (HR=0.
46; 95%CI: 0.
29-0.
73; P=0.
001); PSA50 RR were 22% and 4% (P=0.
014); median OS was 24 months and 21.
3 months (HR= 0.
62; 95%CI: 0.
3-1.
26; P=0.
181)
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Treatment-related adverse events (trAE) were milder and similar in both groups (dalotamide group vs placebo group): G1 was 26% vs 22%, G2 was 13% vs 15%, and G3 was 2% vs 2 %
.

G1/2 fatigue was less common in the dalotamide group (11% vs 20%)
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04 Study conclusions The study showed that maintenance therapy with dalotamide after receiving at least one NHA treatment and taxanes in the past can prolong rPFS and EFS and is well tolerated
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LBA28STAR Study: A randomized multi-phase II/III phase trial comparing intermittent or continuous standard first-line treatment (sunitinib or pazopanib) for locally advanced and/or metastatic renal cell carcinoma (RCC) 01 Research background In the treatment of tumors, reducing toxicity without affecting the efficacy has always been a concern
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The STAR study aims to determine whether intermittent therapy (DFIS) is non-inferior to continuous therapy (CCS) in the first-line treatment of advanced RCC
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The study endpoints were OS and quality-adjusted life year (QALY)
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02 Research method The STAR study is a phase II/III multicenter, randomized controlled trial in the United Kingdom.
Patients were randomly assigned to the DFIS group or the CCS group at a 1:1 ratio
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After 24 weeks of sunitinib or pazopanib treatment, the DFIS group was discontinued until the disease progressed
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The primary endpoint OS and QALY must be confirmed in the intention-to-treat (ITT) and compliance program (PP) analysis in both the pre-set non-inferiority (NI) (≤7.
5% OS; ≤10% QALYs)
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In addition, an economic evaluation was also carried out
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03 Study results From January 13, 2012 to September 12, 2017, a total of 920 patients were enrolled and randomly assigned to the CCS group (n=461) and DFIS group (n=459)
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A total of 488 patients (53.
0%) continued to participate in the trial after 24 weeks of treatment, 240 (52.
1%) vs 248 (54.
0%) in the CCS group vs.
DFIS group
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The median treatment interruption time was 87 days
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The numbers of patients analyzed by ITT and PP were 461 vs 458 and 453 vs 418, respectively
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In the OS analysis, the conclusions are different, and the NI: HR (95%CI) ITT: 0.
97 (0.
83-1.
12); PP: 0.
94 (0.
80-1.
09), NI cut-off value: 95%CI≥0.
812
.

However, consistent NI conclusions can be drawn from the QALY analysis: HR (95%CI) ITT: -0.
05 (-0.
15~0.
05); PP: 0.
04 (-0.
14~0.
21), NI cut-off value: 95%CI≥-0.
156
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After two years of treatment, the cost of DFIS is lower
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04 Research conclusions Although OS failed to reach NI, QALY NI was confirmed and DFIS was considered acceptable among patients and clinicians
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In addition, DFIS is more cost-effective than CCS
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LBA29Navulumab combined with ipilimumab in the first-line treatment of patients with advanced renal cell carcinoma: a randomized phase II trial (PRISM) 01 research background ipilimumab combined with nivolimumab is a medium- to high-risk advanced renal cell The standard first-line treatment for patients with cancer (aRCC)
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During the initial combination therapy, grade 3/4 (G3/4) trAEs are more common
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This randomized phase II trial aims to evaluate whether the improved dosing regimen of ipilimumab combined with nivolumab can reduce side effects without affecting the efficacy
.

02 Research methods The study included patients with untreated renal clear cell carcinoma who were randomized to receive ipilimumab 1 mg/kg Q3W (conventional IPI) or Q12W (modified IPI), combined with nivolumab (3 mg/kg) treatment until the disease progresses or intolerable toxicity occurs
.

The primary endpoint of the study was the proportion of patients with G3/4 trAE within 12 months of starting treatment.
The secondary endpoints included 12-month progression-free survival (PFS) and objective response rate (ORR)
.

The results of the 03 study showed that the G3/4 trAE of patients who received modified IPI was significantly lower than that of patients who received conventional IPI (32.
8% vs 53.
1%; OR 0.
43 [90%CI: 0.
25-0.
72]; P=0.
0075); and the modified protocol There was no significant reduction in ORR or PFS
.

Figure 3 Study results LBA27NORSE study: Erdatinib (ERDA) or ERDA combined with Cetrelimab (CET) in the treatment of locally advanced or metastatic urothelial carcinoma (mUC) patients with fibroblast growth factor receptor mutation (FGFRa) II The first result analysis of the phase study 01 Research background For patients with mUC who are intolerant to cisplatin, immune checkpoint inhibitors are recommended as the first-line treatment
.

The pan-FGFR inhibitor ERDA has proved to have clear benefits in the second-line treatment of mUC patients with FGFRa targeted therapy.
ERDA combined with PD-1 antibody CET can bring new options for the first-line treatment of FGFRa patients
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Phase 1b of the NORSE study determined the tolerable dose of ERDA+CET in the second-line treatment of mUC patients.
This ESMO conference reported part of the results of ERDA as a single agent or combined with CET in the first-line treatment of patients with cisplatin intolerance and FGFR mutant mUC.

.

02Research method The study included patients with FGFRa mutation/fusion mUC and randomly received ERDA 8 mg once a day (UpT to 9 mg) or ERDA 8 mg (without UpT) + IV CET 240 mg once every 2 weeks (1:1).
1-4 cycles), thereafter 480 mg, once every 4 weeks
.

The primary endpoint is the overall response rate (ORR) and safety assessed by the investigator according to RECIST 1.
1.
The secondary endpoints include disease control rate (DCR), time to response (TTR), and duration of response (DOR)
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03 Results of the study As of July 19, 2021, a total of 53 patients were enrolled (26 in the monotherapy group and 27 in the combination therapy group)
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Single-drug vs combination group: median age was 75 vs 69 years, visceral metastasis ratio was 54% vs 52%, ECOG score 0-1 ratio was 77% vs 63%
.

The efficacy and safety data are shown in Figure 4.
The ORR of the single-agent group and the combination group were 33% and 68%, and the DCR were 100% and 90%, respectively
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The most common TRAE is mainly manifested as: hyperphosphatemia, angular cheilitis and diarrhea
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Figure 4 NORSE study data 04 study conclusions The study shows that ERDA+CET has good efficacy and safety in the first-line treatment of cisplatin intolerant FGFRa mutant mUC patients
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References: 1.
Final overall survival (OS) analysis from ARCHES: A phase III, randomized, double-blind, placebo (PBO)-controlled study of enzalutamide (ENZA) + androgen deprivation therapy (ADT) in men with metastatic hormone- sensitive prostate cancer (mHSPC).
2021 ESMO,LBA25.
2.
Darolutamide maintenance in metastatic castration resistant prostate cancer (mCRPC) previously treated with novel hormonal agents (NHA) and non-progressive disease after subsequent treatment with a taxane: A randomized doubleblind placebo -controlled phase II trial (SAKK 08/16).
2021 ESMO,LBA26.
3.
STAR: A randomised multi-stage phase II/III trial of standard first-line therapy (sunitinib or pazopanib) comparing temporary cessation with allowing continuation, in the treatment of locally advanced and/or metastatic renal Cancer (RCC).
2021 ESMO, LBA28.
4.
Nivolumab in combination with alternatively scheduled ipilimumab in first-line treatment of patients with advanced renal cell carcinoma: A randomized phase II trial (PRISM).
2021 ESMO,LBA29.
5.
Erdafitinib (ERDA) or ERDA plus cetrelimab (CET) for patients with metastatic or locally advanced urothelial carcinoma (mUC) and Fibroblast Growth Factor Receptor alterations (FGFRa): First phase (Ph) II results from the NORSE study.
2021 ESMO,LBA27.
LBA27.
LBA27.