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

Abstract

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...

Current Treatment and Outcomes Benchmark for Locally Advanced or Metastatic Urothelial Cancer From a Large UK-Based Single Centre

“…Just under half of these patients received single-agent weekly paclitaxel. The low uptake of second-line therapy, consistent with previous reports (26), may in part reflect the low response rates and short duration of response associated with these agents (27). Second-line chemotherapy at our center has typically been reserved for fit patients or those with symptomatic disease progression and following careful FIGURE 3 | Cox regression analysis comparing cisplatin-based (blue) and carboplatin-based (red) sub-cohorts, adjusted for age, sex, PS, and confirmed metastasis.…”

“…Fisher et al recently reported median OS of 14.6 months with cisplatin and 11.3 months with carboplatin, in a real-world US setting (25). A 16.1 month median OS was reported in a retrospective German study of patients with stage IV UC treated with chemotherapy (26). Whilst the proportion of M1 patients varied between studies, overall our survival is remarkably similar and highlights the need to improve outcomes for this group of patients.…”

Survival Benefit for Patients With Metastatic Urothelial Carcinoma Receiving Continuous Maintenance Chemotherapy

“…The median survival time for our MUC patients receiving continuous maintenance chemotherapy was 17 months, with no difference between bladder and upper urinary tract cancer location (18 versus 17 months). The survival time was compatible with previous reports (1,13,14). Patient survival was likely related not only to the objective tumor response, but also to inflammation and coagulopathy as major contributory factors to patient death, as demonstrated by the inflammation-related symptoms and cause of death.…”

Timing of changing therapy from gemcitabine and cisplatin chemotherapy based on real‑world data of advanced urothelial carcinoma

“…Urothelial carcinoma (UC) is the most common cancer of the bladder and upper urinary tract and is invasive and lethal, especially in advanced and metastatic patients (1,2). Advanced UC patients generally have a poor prognosis, and only a few patients survive more than five years (3).…”