Clinical Trials Corner

Dear Readers,

The Clinical Trials Corner of the Bladder Cancer journal is a section devoted towards highlighting ongoing trials or recently completed trials in urothelial cancer. Our hope is to encourage accrual for ongoing trials and to educate readers on the results of completed trials. If you feel that you would like to draw attention to a specific trial, please feel free to email us at: pkagarwal@uchicago.edu and/or cns9006@med.cornell.edu.

Sincerely,

Piyush K. Agarwal Cora N. Sternberg
Piyush K. Agarwal, MD Cora N. Sternberg, MD, FACP
Associate Editor, Bladder Cancer Associate Editor, Bladder Cancer
Director, Bladder Cancer Program Clinical Director, Englander Institute of Precision Medicine
University of Chicago Medicine Weill Cornell Medicine
Chicago, IL, USA New York, NY, USA

Phase II Open Label, Study of IMMU-132 in Metastatic Urothelial Cancer After Failure of Platinum-Based Regimen or Anti-PD-1/ PD-L1 Based Immunotherapy (TROPHY-U-01 Cohort 1)

Status: 
Open
Sponsor: 
Immunomedics, Inc.
Enrollment: 
201
Study Design: 
This was a phase II, multicenter single-arm trial and updated data for the cohort of 113 patients with metastatic UC that progressed on prior platinum and immune checkpoint therapy were presented at ESMO 2020. Patients received IMMU-132 10mg/kg days 1 and 8 of a 21-day cycle that was continued until toxicity or disease progression. The null hypothesis was an overall response rate 12%.
Rationale: 
Although patients with metastatic UC have multiple options for therapy, patients who do not respond to platinum-based chemotherapy and/or anti-PD-1/PD-L1 based immunotherapy have had few treatment options until recently (enfortumab vedoin and erdafitinib). Antibody-drug conjugates (ADCs) are monoclonal antibodies (mABs) conjugated to cytotoxic drugs that can deliver a toxic payload to tumor cells expressing a specific tumor target. Enfortumab vedotin is a well-known ADC targeting Nectin 4 that is now FDA-approved. In this specific trial, a different ADC, Sacituzumab govitecan (SG), also known as IMMU-132, is evaluated containing an antibody against the epithelial cell surface molecule Trop-2 conjugated SN-38 (a potent derivative of the cytotoxic drug irinotecan). Trop-2 is overexpressed in bladder cancer and SN-38 inhibits DNA topoisomerase 1 thereby preventing DNA unwinding which results in irreversible double strand DNA breaks and eventually cytotoxic cell death. SG is distinct from other ADCs, with a high drug-to-antibody ratio.
Endpoints: 
The primary objective was overall response rate (ORR) and the secondary outcomes are duration of response (DOR), PFS and OS.
Comments: 
The results are encouraging given the fact that the patients were heavily pre-treated. In fact, 10 patients in the cohort were previously treated with enfortumab vedotin and despite that 3 of these patients had a partial response to SG. ADCs may represent a new salvage therapy option for patients with metastatic UC with progression after checkpoint inhibition therapy and chemotherapy.
Results: 
The group was heavily pre-treated with a median number of 3 prior anti-cancer therapies and the median age of the cohort was 66. There was a 27% overall response rate. The median duration of response was 5.9 months and 76% of patients had a reduction in tumor size. As of data cut-off, 16 of the 113 patients were continuing on treatment. Overall two-thirds of patients discontinued therapy due to progressive disease. Median PFS was 5.4 months and median OS was 10.5 months. Of note, 28% of patients had liver metastases. The most common treatment-related adverse event was diarrhea with 9% of patients having a grade 3 event.

Phase II multicenter, randomized study to evaluate efficacy and safety of avelumab with carboplatin/gemcitabine (CG) vs CG alone in patients with unresectable or metastatic urothelial carcinoma (mUC) who are ineligible to receive cisplatin-based therapy (

Status: 
Open
Sponsor: 
Associació per a la Recerca Oncologica, Spain
Enrollment: 
85
Study Design: 
This is a phase II multicenter, randomized trial evaluating the safety and efficacy of the combination of avelumab plus carboplatin/ gemcitabine versus carboplatin/ gemcitabine alone in patients with metastatic UC who have not received prior systemic therapy and are cisplatin ineligible. Patients had to have an ECOG status of 0-2 and patients received 6 cycles of carboplatin/gemcitabine with or without avelumab which was given as induction (2 cycles avelumab), concurrent with chemotherapy (6 cycles), and as maintenance in the group that received it with the chemotherapy. Avelumab maintenance was continued until progression, unacceptable toxicity, or treatment discontinuation.
Rationale: 
Up to 50% of patients with metastatic urothelial carcinoma (mUC) are not eligible for cisplatin. Carboplatin has activity but not comparable and so this trial evaluates whether Avelumab given as an induction therapy and in combination with carboplatin/ gemcitabine results in superior anti-tumor activity compared to standard chemotherapy in cisplatin-ineligible patients with metastatic UC. Biologically, chemotherapies can induce immunogenic cell death which may enhance the ability of checkpoint inhibitors such as avelumab.
Endpoints: 
The primary endpoint was overall response rate (ORR) by RECIST criteria. The secondary endpoints included PFS, OS, duration of response (DoR), and safety and tolerability.
Comments: 
Induction immunotherapy followed by chemoimmunotherapy did not significantly improve outcomes in this trial. The trial is different than the findings seen in the Javelin 100 study which demonstrated superior OS in the maintenance arm with avelumab. However, this initial analysis is still immature and further follow-up is needed for definitive conclusions.
Results: 
The trial enrolled 42 patients in the chemoimmunotherapy arm and 42 patients in the chemotherapy alone arm. In an intention to treat analysis, the overall response rate was 57.1% versus 53.5% respectively, with no significant difference between the arms. Partial and complete responses were 45.2% and 11.9% in the chemoimmunotherapy arm compared with 44.2% and 9.3% in the chemotherapy arm. Median PFS was similar at 6.9 months versus 7.4 months (p=0.1356) in the chemoimmunotherapy versus chemotherapy arms respectively. Median OS was similar at 10.5 months versus 13.2 months (p=0.2642) in the chemoimmunotherapy versus chemotherapy arms respectively. Overall, the drugs were safe and tolerable with their usual expected toxicities.

A phase 3 randomized open label study of durvalumab with or without tremilumimab versus standard of care (SoC) chemotherapy in patients with unresectable, locally advanced or metastatic urothelial carcinoma (DANUBE)

Status: 
Open
Sponsor: 
AstraZeneca
Enrollment: 
1032
Study Design: 
DANUBE is a randomized, phase 3 trial to evaluate durvalumab, with or without tremelimumab, vs platinum-based chemotherapy as a first-line treatment for metastatic UC. Patients were randomized 1:1:1 to Durvalumab 1500 mg q4w alone until progression (n=346) or Durvalumab plus Tremelimumab 75 mg q4w for up to 4 doses (n=342) or SoC chemotherapy (gemcitabine + cisplatin or carboplatin, up to 6 cycles) (n=344.)
Rationale: 
Platinum-based chemotherapy is the standard of care (SoC) for first-line treatment of metastatic UC. While chemotherapy regimens yield high response rates, survival outcomes are poor. Durvalumab (anti-PD-L1) is FDA approved for the treatment of platinum-refractory, metastatic UC. Tremelimumab (anti-CTLA-4) and the combination of durvalumab plus tremelimumab have shown activity in platinum-refractory, metastatic UC regardless of PD-L1 expression.
Endpoints: 
The co-primary endpoints were OS comparing durvalumab monotherapy vs. chemotherapy groups among patients whose tumors had high PD-L1 expression and overall survival comparing durvalumab + tremelimumab vs. chemotherapy groups in the intention-to-treat (ITT) population.
Comments: 
The primary endpoints in his study were not met. With a median follow-up for survival of 41.2 months, this study has the longest follow-up to date for a randomized trial of an immunotherapy in previously untreated, metastatic UC. Further investigation of the combination in the context of checkpoint inhibitors may be warranted.
Results: 
The DANUBE trial did not meet either of the co-primary endpoints of overall survival. However, secondary analyses suggested that the combination of durvalumab + tremelimumab has activity, which is enhanced in patients with tumours that have high PD-L1 expression. This trial was a negative trial but it does suggest that a biomarker-based strategy should be tested in patients whose tumors are PD-L1 positive and may benefit from the combination of durvalumab + tremelimumab.

Pembrolizumab alone or combined with chemotherapy versus chemotherapy alone as first line therapy for advanced urothelial carcinoma (UC): Keynote 361

Status: 
Open
Sponsor: 
Merck Sharpe and Dohme
Enrollment: 
1010
Study Design: 
This was a global, randomized open label phase 3 trial comparing pembrolizumab alone or combined with platinum-based chemotherapy versus chemotherapy as first line treatment for patients with locally advanced or metastatic UC. Patients were randomized 1:1:1 to pembrolizumab and chemotherapy (n=351) or pembrolizumab alone (n= 307) or chemotherapy alone (n=352).
Rationale: 
The current standard for first line treatment in advanced UC is cisplatin-based chemotherapy. Pembrolizumab is recommended for patients as second line therapy or as first line therapy in patients that are PDL-1 positive and ineligible for platinum. Avelumab is recommended as maintenance treatment for patients who do not progress on first line chemotherapy.
Endpoints: 
There were dual primary endpoints, progression free survival (PFS) per RECIST by blinded independent review and overall survival (OS).
Comments: 
The results of this trial were unexpected as pembrolizumab is approved for metastatic disease as well as BCG unresponsive non-muscle invasive bladder cancer. The results seem to close the door for combination chemotherapy and immunotherapy in the front-line setting. In a somewhat similar study with atezolizumab, the combination led to improvement in PFS, but OS has yet to be reported.
Results: 
The combination of immunotherapy and chemotherapy did not reach statistical significance for PFS or OS in patients with untreated locally advanced or metastatic UC.

Maintenance avelumab + best supportive care (BSC) versus BSC alone after platinum-based first-line chemotherapy in advanced urothelial carcinoma: JAVELIN Bladder 100 phase III results

Status: 
Open
Sponsor: 
Merck and Pfizer Inc
Enrollment: 
700
Study Design: 
Patients with unresectable locally advanced or metastatic UC treated with Cisplatin + gemcitabine or Carboplatin + gemcitabine chemotherapy (4-6 cycles) and obtained a CR, PR, or SD that was maintained for 4-10 weeks were entered into the study. They were randomized (1:1) between IV Avelumab (anti PDL-1) given every 2 weeks or best supportive care.
Rationale: 
Platinum-based combination chemotherapy has remained the standard-of-care as first-line treatment for advanced urothelial carcinoma (UC). However, durations of progression-free survival (PFS) and overall survival (OS) are limited by chemotherapy resistance
Endpoints: 
The primary endpoint was overall survival. Primary analysis populations included all randomized patients and separately the PD-L1+ population. Secondary endpoints included PFS and objective response per RECIST 1.1, Safety and tolerability and patient reported outcomes.
Comments: 
This Late Breaking Abstract was presented at the ASCO plenary session. Switch maintenance avelumab significantly prolonged overall survival vs best supportive care alone in selected patients with UC whose disease had not progressed on first line platin based chemotherapy. These results are practice changing. Based on these results, this concept has already been approved by the FDA on June 30, 2020.
Results: 
Maintenance avelumab significantly prolonged overall survival compared to best supportive care alone. The overall survival at 1 year was 71.3% vs 58.4%, and median overall survival was 21.4 vs 14.3 months (HR 0.69; 95% CI, 0.56, 0.86; 1-sided P<0.001). Avelumab also significantly prolonged overall survival in the PD-L1+ population as the overall survival at 1 year was 79.1% vs 60.4% (HR 0.56; 95% CI, 0.40, 0.79; 1-sided P<0.001). Adverse events occurred in 98.0% of patients in the avelumab arm and 77.7% of patients in the best supportive care alone arm, including grade ≥3 events in 47.4% and 25.2%, respectively.

A Phase III, Open-Label, Multicenter, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) Versus Observation as Adjuvant Therapy in Patients With High-Risk Muscle-Invasive Urothelial Carcinoma After Surgical Resection

Status: 
Open
Sponsor: 
National Cancer Institute/Canadian Cancer Trials Group and Southwest Oncology Group
Enrollment: 
202
Study Design: 
This is a single-arm Phase II trial in which patients with BCG-unresponsive high-grade non-muscle muscle invasive bladder cancer (CIS ± Ta/T1 OR Ta/T1) received one year of atezolizumab anti PDL-1 therapy intravenously every 3 weeks x 17 cycles. Patients were evaluated every 3 months with cystoscopy and cytology with a mandatory biopsy done at 6 months.
Rationale: 
Immunotherapy and in particular anti PD-1 and anti PD-L1 therapies have demonstrated efficacy in metastatic urothelial cancer and in muscle-invasive bladder cancer. Therefore, these drugs are now being evaluated alone or in combination with other agents in BCG-unresponsive non-muscle invasive bladder cancer. The PD1 inhibitor pembrolizumab was approved in January 2020 and this trial is the first reporting results of a PD-L1 inhibitor (atezolizumab) in this high risk patient population.
Endpoints: 
The primary endpoint of the trial was the pathological CR rate at 6 months in patients with BCG-unresponsive CIS determined by a mandatory biopsy. The secondary endpoints included: 18-month event-free survival in the Ta/T1 cohort, progression-free survival in all patients, cystectomy-free survival in all patients, bladder-cancer specific survival in all patients, and overall survival in all patients.
Comments: 
The trial is a herculean effort to treat non-muscle invasive bladder cancer with systemic immunotherapy. Unfortunately, the strict statistical criteria for closure of this trial led to its falling short of its primary endpoint as the expectation of novel therapies in this disease space should provide a higher 6-month CR rate in patients with CIS. However, the 42% 3-month CR noted was similar to that seen with pembrolizumab which has been FDA-approved although the duration of response for atezolizumab is still pending at this time.
Results: 
The trial launched in 2017 but had a required futility analysis after 25 eligible CIS patients reached the 6 month-endpoint. In order to proceed, at least 7 patients had to have a CR and only 5 patients actually achieved a CR, so the trial was closed to accrual. Ultimately, 172 patients at 68 centers were enrolled of which 128 were eligible: 74 CIS ± Ta/T1 and 54 Ta/T1 without CIS. The CR rate at 6 months in CIS patients was 27% which fell below the null hypothesis of 30%. Of note, the CR rate at 3 months was 42% but this was an unplanned secondary endpoint. Toxicity data is yet unavailable but at least 9 patients in the CIS ± Ta/T1 cohort encountered grade 3-5 AEs during the course of the trial.

Phase II Trial of Atezolizumab in BCG-Unresponsive Non-Muscle Invasive Bladder Cancer (SWOG 1605)

Status: 
Open
Sponsor: 
National Cancer Institute/Canadian Cancer Trials Group and Southwest Oncology Group
Enrollment: 
202
Study Design: 
This is a single-arm Phase II trial in which patients with BCG-unresponsive high-grade non-muscle muscle invasive bladder cancer (CIS ± Ta/T1 OR Ta/T1) received one year of atezolizumab anti PDL-1 therapy intravenously every 3 weeks x 17 cycles. Patients were evaluated every 3 months with cystoscopy and cytology with a mandatory biopsy done at 6 months.
Rationale: 
Immunotherapy and in particular anti PD-1 and anti PD-L1 therapies have demonstrated efficacy in metastatic urothelial cancer and in muscle-invasive bladder cancer. Therefore, these drugs are now being evaluated alone or in combination with other agents in BCG-unresponsive non-muscle invasive bladder cancer. The PD1 inhibitor pembrolizumab was approved in January 2020 and this trial is the first reporting results of a PD-L1 inhibitor (atezolizumab) in this high risk patient population.
Endpoints: 
The primary endpoint of the trial was the pathological CR rate at 6 months in patients with BCG-unresponsive CIS determined by a mandatory biopsy. The secondary endpoints included: 18-month event-free survival in the Ta/T1 cohort, progression-free survival in all patients, cystectomy-free survival in all patients, bladder-cancer specific survival in all patients, and overall survival in all patients.
Comments: 
The trial is a herculean effort to treat non-muscle invasive bladder cancer with systemic immunotherapy. Unfortunately, the strict statistical criteria for closure of this trial led to its falling short of its primary endpoint as the expectation of novel therapies in this disease space should provide a higher 6-month CR rate in patients with CIS. However, the 42% 3-month CR noted was similar to that seen with pembrolizumab which has been FDA-approved although the duration of response for atezolizumab is still pending at this time.
Results: 
The trial launched in 2017 but had a required futility analysis after 25 eligible CIS patients reached the 6 month-endpoint. In order to proceed, at least 7 patients had to have a CR and only 5 patients actually achieved a CR, so the trial was closed to accrual. Ultimately, 172 patients at 68 centers were enrolled of which 128 were eligible: 74 CIS ± Ta/T1 and 54 Ta/T1 without CIS. The CR rate at 6 months in CIS patients was 27% which fell below the null hypothesis of 30%. Of note, the CR rate at 3 months was 42% but this was an unplanned secondary endpoint. Toxicity data is yet unavailable but at least 9 patients in the CIS ± Ta/T1 cohort encountered grade 3-5 AEs during the course of the trial.

A Phase 3 Multicenter Trial Evaluating the Efficacy and Safety of MitoGel™ on Ablation of Upper Urinary Tract Urothelial Carcinoma (The OLYMPUS Study – Optimized DeLivery of Mitomycin for Primary Upper Tract Urothelial Carcinoma Study)1

Status: 
Closed
Sponsor: 
UroGen Pharma Ltd.
Enrollment: 
71
Study Design: 
This was a prospective, multicenter open-label single-arm trial evaluating the safety, efficacy, and tolerability of MitoGel instilled into the upper urinary tract of patients with non-invasive low-grade (LG) UTUC. Patients had to have at least one measurable papillary tumor. Patients were treated once weekly for 6 weeks by retrograde instillation. Safety and Efficacy was evaluated approximately 5 weeks following the last instillation, roughly 11 weeks after enrollment, by direct inspection of the upper tract, biopsies of any tumors, and upper tract washed urine cytology. Patients who achieved a CR at 3 months were treated with monthly maintenance therapy for a total of 11 instillations or up to the first recurrence whichever came first.
Rationale: 
Unlike bladder urothelial carcinoma, upper tract urothelial carcinoma (UTUC) has not been successfully treated with instillation therapy with chemotherapy or immunotherapy. Although some case reports describe instillation therapy into the upper urinary tract delivered through nephrostomy tubes, there has not been a reliable and convenient method of delivery until now. This trial uses a novel formulation of mitomycin C (MitoGel, now named JELMYTO) that can be instilled in a liquid form which can solidify at body temperature into a gel that can allow dwell times of several hours in the upper urinary tract. Mitomycin C is an alkylating agent that inhibits the transcription of DNA into RNA thereby preventing protein synthesis and inhibiting growth of cancer cells. It has shown to be effective in urothelial cancer of the bladder.
Endpoints: 
The primary endpoint was the complete response (CR) rate at 3 months. Secondary endpoints included the CR rate at 12 months. The mitomycin C level was also evaluated in the plasma of a subgroup of the patients.
Comments: 
This is the first trial exclusively for upper tract urothelial cancer and it establishes the first FDA-approved therapy in this rare, “orphan,” disease. In addition, the therapy was effective in patients without complete resection/ablation of existing papillary tumors. However, the response rate was only durable at 12 months in approximately 20% (14 of 71) of the patients and was limited to only those patients with LG disease. Given the inaccuracies with grading and staging of upper tract urothelial cancer based on small volume biopsies, it is also conceivable that some patients with high grade disease may be inadvertently treated with this approach which may not be effective. Nevertheless, this trial has paved the way for localized therapies for UTUC.
Results: 
This study demonstrated a CR rate of 59% (42 patients) at 3 months. Nineteen of these patients (46%) maintained a CR at 12 months. The most frequent adverse events included ureteric stenosis (44%), urinary tract infection (32%), hematuria (31%), flank pain (30%), and nausea (24%). Of note, of the patients who developed ureteric obstruction, 51% had some level of persistent obstruction.

A Phase III Randomised Trial of Peri-Operative Chemotherapy Versus Surveillance in Upper Tract Urothelial Cancer (POUT Study)2

Status: 
Closed
Sponsor: 
Institute of Cancer Research, United Kingdom
Enrollment: 
261
Study Design: 
This was a phase III, multi-center open-label randomized controlled trial in which patients who had undergone nephroureterectomy for UTUC, with pT2-T4, N0 disease or pTany N1-3 M0 disease, and fit for adjuvant chemotherapy, were randomized (1:1) to either four cycles of platinum-based adjuvant chemotherapy or surveillance. Patients with microscopically positive margins on pathology were permitted as long as all gross disease was resected. Chemotherapy consisted of four 21-day cycles of gemcitabine-cisplatin, however, in patients with GFR 30-49 mL/min, carboplatin was substituted for cisplatin and was initiated within 90 days of surgery.
Rationale: 
The benefit of peri-operative chemotherapy for urothelial cancer of the bladder is well established for neoadjuvant therapy and less so for adjuvant therapy due to the difficulties in accrual to many of these trials. Although UTUC is related to urothelial cancer of the bladder, the role of chemotherapy and the proper sequencing of surgery with chemotherapy in UTUC is largely unknown and frequently extrapolated from the management of bladder cancer. This trial specifically evaluates the impact of adjuvant chemotherapy given after nephroureterectomy for high grade UTUC.
Endpoints: 
The primary endpoint of the trial was disease-free survival (DFS) at three years. The secondary endpoints included overall survival, metastasis-free survival, incidence of bladder second primary tumors, incidence of contralateral primary tumors, acute and late toxicity, treatment compliance, and quality of life.
Comments: 
Although renal function may be less optimal after nephroureterectomy, the rationale of adjuvant chemotherapy is that it would minimize overtreatment given more accurate staging with final pathology. However, many patients (estimated to be up to a third) will be ineligible for cisplatin-based adjuvant chemotherapy (GFR<50 mL/min) and subset analysis demonstrated no benefit with carboplatin-based chemotherapy. Nevertheless, this trial firmly establishes the benefit and role of adjuvant gemcitabine-cisplatin in patients with GFR>50 mL/min. This trial does not address neoadjuvant chemotherapy which conceivably would be more tolerable to patients (given better renal function with both kidneys in place) and demonstrates excellent overall survival from retrospective series. However, the risk of over-treatment of patients with neoadjuvant chemotherapy is significant given that chemotherapy is based on limited staging information obtained from ureteroscopic biopsies.
Results: 
Ultimately, 132 patients were assigned chemotherapy and 129 were assigned surveillance. Adjuvant chemotherapy significantly improved DFS (HR = 0.45, 95% CI 0.3-0.68, p=0.0001) at a median follow-up of 30.3 months with 3-year DFS estimates of 71% (chemotherapy) vs. 46% (surveillance). In addition, the metastasis-free survival rate at two years was 74% vs. 60% for chemotherapy vs. surveillance patients (p=0.002), respectively. However, overall survival was not significantly different between the groups in the early published analysis. On subset analysis, chemotherapy did not demonstrate a benefit in lymph node positive patients or patients with microscopic positive margins. Most importantly, subset analysis did not show a benefit with gemcitabine-carboplatin chemotherapy. Among all chemotherapy-treated patients, 44% had acute grade 3 or greater treatment-related adverse events (TRAEs). This is in comparison to a 4% acute grade 3 or greater TRAEs in the surveillance patients.

A Phase III, Open-Label, Multicenter, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) Versus Observation as Adjuvant Therapy in Patients With High-Risk Muscle-Invasive Urothelial Carcinoma After Surgical Resection.

Sponsor: 
Hoffmann-La Roche
Enrollment: 
809
Study Design: 
This is a phase III, multicenter open-label trial that randomly assigned patients with muscle-invasive urothelial cancer after surgical resection with high risk features for recurrence to either observation or adjuvant atezolizumab treatment in a 1:1 fashion. Patients randomized to intravenous atezolizumab received therapy with 1200 mg every 3 weeks for up to 16 cycles. Patients with pT2-T4 disease after neoadjuvant chemotherapy, or pT3-4 disease without neoadjuvant chemotherapy, or any node positive disease after radical cystectomy were considered high risk for recurrence and eligible for the trial. Assessment of tumor status was performed by radiographic imaging prior to initiation of treatment.
Rationale: 
Patients with high-risk muscle invasive urothelial cancer after surgical resection have limited options for treatment. Historically, they have been observed only to later develop local or systemic recurrences and to eventually succumb to urothelial cancer. However, with the absence of a proven benefit of adjuvant therapy and dearth of treatments except for chemotherapy, there has been little progress in this disease space of urothelial cancer. This trial, also known as the IMvigor010 trial, aimed to evaluate the impact of adjuvant atezolizumab, a PD-L1 inhibitor, in patients randomized to receiving such therapy after radical cystectomy with high risk features seen on pathology.
Endpoints: 
Primary outcome was disease-free survival (DFS) from the time of randomization and included pelvic (local) recurrence, extravesical urinary tract recurrence, distant metastases, or death from any cause. Secondary outcomes included overall survival, disease-specific survival, disease metastasis-free survival, and non-urinary tract recurrence-free survival.
Comments: 
This trial unfortunately did not demonstrate a difference in DFS with the use of adjuvant atezolizumab. One of the criticisms is that this trial may have excluded patients likely to benefit and included patients unlikely to benefit with atezolizumab. Patients with positive surgical margins are most likely to recur with local (pelvic) recurrence and may benefit most from adjuvant therapy but were excluded from this trial. Another potential issue is potentially that there may be a difference in efficacy between PD-1 and PD-L1 inhibitors as PD-1 inhibitors have demonstrated slightly better survival results in some studies although no studies have directly compared these two different types of inhibitors.
Results: 
In this trial, Atezolizumab failed to meet the primary end point, disease-free survival (DFS), as adjuvant monotherapy in patients with muscle-invasive urothelial cancer (MIUC) compared with observation in the phase III IMvigor010 clinical trial, according to a press release from Roche, developer of the drug on January 24, 2020 (https://bit.ly/38zdRoE)

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