Safety and Efficacy of Atezolizumab in Understudied Populations with Pretreated Urinary Tract Carcinoma: Subgroup Analyses of the SAUL Study in Real-World Practice.

PURPOSE: Atezolizumab is an established treatment option for pretreated urothelial carcinoma, demonstrating efficacy in phase II/III trials. The SAUL study enrolled a broader patient population to determine safety and efficacy in underrepresented subgroups. MATERIALS AND METHODS: Patients with metastatic urinary tract carcinoma received atezolizumab 1,200 mg every 3 weeks until disease progression, unacceptable toxicity, loss of clinical benefit, or patient/physician decision. The primary endpoint was safety. Efficacy was a secondary endpoint. Analyses by programmed cell death ligand-1 (PD-L1) status, age, Eastern Cooperative Oncology Group performance status (ECOG PS) and renal impairment were prespecified; post hoc analyses explored outcomes by tumor location. RESULTS: A total of 1,004 patients were enrolled. Subgroup analyses in patients with older age, renal impairment, or upper tract urothelial carcinoma showed safety and efficacy similar to those in patients without these characteristics. Patients with ECOG PS 2 had clinical features typically associated with aggressive disease; median overall survival was 2.3 months versus 10.0 months in patients with ECOG PS0/1. Patients with PD-L1 expression on ≥5% of tumor-infiltrating immune cells tended to have better outcomes than those with <5% PD-L1 expression, although conclusions on the relative efficacy of atezolizumab cannot be drawn from this single-arm study. CONCLUSIONS: The understudied populations included in the SAUL study had similar outcomes to those in more selected populations included in phase II/III trials of atezolizumab, except for those with ECOG PS 2. Age ≥80 years and/or creatinine clearance <30 ml/minute does not preclude administration of atezolizumab; however, treatment risk versus benefit must be carefully assessed in patients with ECOG PS 2.

Partial Response and Stable Disease Correlate with Positive Outcomes in Atezolizumab-treated Patients with Advanced Urinary Tract Carcinoma.

BACKGROUND: The value of a complete response to immune checkpoint inhibitor treatment for urothelial cancer is well recognised, but less is known about long-term outcomes in patients with a partial response or the benefit of achieving disease stabilisation. OBJECTIVE: To determine clinical outcomes in patients with a partial response or stable disease on atezolizumab therapy for advanced urinary tract carcinoma (UTC). DESIGN, SETTING, AND PARTICIPANTS: Data were extracted from three prospective trials (IMvigor210 cohort 2, SAUL, and IMvigor211) evaluating single-agent atezolizumab therapy for platinum-pretreated advanced UTC. The analysis population included 604 atezolizumab-treated and 208 chemotherapy-treated patients (229 achieving a partial response and 583 achieving stable disease). INTERVENTION: Atezolizumab 1200 mg every 3 wk until progression or unacceptable toxicity or single-agent chemotherapy for patients in the control arm of IMvigor211. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Baseline characteristics, treatment exposure, overall survival, duration of disease control. Partial response and stable disease populations were analysed separately. RESULTS AND LIMITATIONS: The population of patients with a partial response included more patients with programmed cell death ligand 1 (PD-L1) expression on ≥5% of tumour-infiltrating immune cells than the stable disease population. The median time to best response was 2.1 mo across trials and treatments, regardless of the type of response. Atezolizumab-treated patients with a partial response had sustained disease control (median overall survival not reached); durations of disease control and overall survival were longer with atezolizumab than with chemotherapy. In patients with stable disease, median overall survival was numerically longer with atezolizumab (exceeding 1 yr) than with chemotherapy. Irrespective of treatment, durations of disease control and survival were shorter in patients with stable disease than in those achieving a partial response. These analyses are limited by their post hoc exploratory nature and relatively short follow-up. CONCLUSIONS: Stable disease and partial response are meaningful clinical outcomes in atezolizumab-treated patients with advanced UTC. PATIENT SUMMARY: In this report, we looked at the outcomes in patients whose tumours responded to treatment to some extent, but the tumour did not disappear completely. We aimed to understand whether a modest response to treatment was associated with meaningful long-term outcomes for patients. We found that on average, life expectancy was >1 yr in patients whose disease was stabilised and even longer in those whose tumours showed some shrinkage in response to treatment.

A Real-World Data Study to Evaluate Treatment Patterns, Clinical Characteristics and Survival Outcomes for First- and Second-Line Treatment in Locally Advanced and Metastatic Urothelial Cancer Patients in Germany.

Background: Worldwide, urothelial carcinoma (UC) is a common cause of morbidity and mortality. In particular, the incidence of bladder cancer varies widely across Europe; Germany has the ninth highest international age-standardized incidence. For advanced UC or metastatic UC (mUC), platinum-based combination chemotherapy is the standard first-line (1L) treatment; however, there is wide heterogeneity of second-line (2L) treatments, ranging from vinflunine in parts of Europe to taxanes and other agents elsewhere in Europe, in the United States and globally. Limited data exist on treatment patterns and outcomes in patients with advanced UC or mUC in the routine clinical setting in Germany. The objective of this study was to describe clinical characteristics, treatment patterns and subsequent outcomes in this setting. Methods: This retrospective observational cohort analysis evaluated 1L and 2L treatment patterns and overall survival (OS) in patients aged ≥18 years with advanced UC or mUC (T4b, N2-3 and/or M1) at office-based urology and academic as well as nonacademic urology clinics throughout Germany between 1 November 2009 and 2 June 2016. Data were obtained through the GermanOncology database and additional treatment centers using similar electronic case report forms. Results: Among the 435 patients included in the analysis, 435 received 1L treatment and 125 received 2L treatment. Median age at start of 1L treatment was 69 years, 75% of patients were male, 75% were current or ex-smokers, 15% had hemoglobin <10 g/dL and 44% had creatinine clearance<60 mL/min/1.73; proportions were similar with 2L treatment. Cardiovascular disease was the most frequently reported comorbidity (65%), followed by diabetes (19%). Most patients (77%) received 1L platinum-based combination treatment (most commonly gemcitabine + cisplatin, 83%). Of those treated with 2L treatment, 66% received a single agent (most commonly vinflunine, 71%). Median OS (95% CI) with 1L treatment was 16.1 months (13.7-19.2) overall and 17.7 months (14.4-24.2) with 1L cisplatin + gemcitabine. In the 1L setting, 12-month OS was 61%, 24-month OS was 39% and 36-month OS was 26%. Median (95% CI) OS with 2L treatment was 9.2 months (5.5-11.6) overall and 5.9 months (4.1-12.6) with 2L vinflunine. In the 2L setting, OS rates for the same time periods were 40%, 22% and 8%, respectively. Median (95% CI) progression-free survival was 7 months (6.4-8.1) and 4 months (3.0-4.8), respectively, in the 1L and 2L settings. Objective response rates were 34% in the 1L setting and 14% in the 2L setting. No difference in OS by sex or smoking status was noted. Patients with or without renal impairment had a 12-month OS of 54% or 69%, respectively. OS at 12 months was 63% among patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1 vs 53% among patients with an ECOG PS of ≥2. Cox regression analysis found no difference in OS between vinflunine and other 2L treatments (P = 0.69). Conclusions: This study provides a contemporary multicenter assessment of real-world treatment patterns and outcomes among palliatively treated patients with UC in Germany. The findings were generally consistent with the poor treatment outcomes observed globally, underscoring the need for effective 1L and 2L treatment for advanced UC or mUC.