Current Systemic Treatment Options in Metastatic Urothelial Carcinoma after Progression on Checkpoint Inhibition Therapy—A Systemic Review Combined with Single-Group Meta-Analysis of Three Studies Testing Enfortumab Vedotin

Deininger, Susanne; Törzsök, Péter; Oswald, David; Lusuardi, Lukas

doi:10.3390/cancers13133206

Cited by 7 publications

(8 citation statements)

References 78 publications

(108 reference statements)

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“…Limited data are available on the effectiveness of these treatment options in such patients. A recent publication in muBC patients who showed disease progression following immune checkpoint inhibition, supports the use of the antibody-drug-conjugate enfortumab vedotin (72). Several studies of novel combinations of immune checkpoint inhibitors with other agents are ongoing; thus, we anticipate a continuous and rapid evolution of the treatment landscape of metastatic bladder and kidney cancer.…”

Section: Radiotherapy Combined With Novel Anticancer Agentsmentioning

confidence: 93%

Radiotherapy in Metastatic Urothelial Carcinoma: Rationale and Clinical Applications

et al. 2022

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Urothelial carcinoma is the most common type of bladder cancer including upper urinary tract urothelial cell carcinoma (renal pelvis and ureters) and urethral carcinoma. It exhibits high mortality and morbidity rates and is usually diagnosed at a late, incurable stage, carrying a poor prognosis. Local symptoms in patients with metastatic urothelial carcinoma (mUC) have an adverse impact on quality of life (QoL) and are associated with frequent hospitalizations. Herein, we review the role of palliative radiotherapy in mUC as the means to ameliorate a wide range of symptoms, seeking optimum patient stratification, even though the latter should be balanced against any acute or late toxicity that may arise. For this, links to the molecular biology of mUC are explored and QoL assessments are presented. To maximize patient benefit from radiotherapy, we conclude that multi-modal datasets need to be re-visited to better inform multi-center studies where policy makers, health professionals, researchers, and patient groups meet. Radiotherapy either as a monotherapy or alongside systemic therapy may serve as an added value.Urothelial carcinoma (UC) is considered as the most common tumor type that arises from the urinary tract and may present either as bladder carcinoma (BC), upper urinary tract urothelial cell carcinoma (UTUC), or urethral carcinoma (1). BC has been reported as the 10th most common cancer worldwide in 2020 and the 6th most common tumor type in the USA, occurring mainly in older people, with a median age at diagnosis of 73 years (2-4). In developed countries, UTUC shows a lower incidence than that of BC and the ratio of the UC incidence in the renal pelvis, ureter, and bladder is approximately 3: 1: 51 (5, 6). About 25% of patients with UC present with metastatic disease. The 5-year survival for this group of patients is only 7.7% (SEER statistics; 2, 3, 7, 8).Systemic therapy remains the cornerstone in the management of patients with mUC. Prior to the development of effective chemotherapy, median survival for mUC patients rarely exceeded 3 to 6 months (9). In the last few years, a revolution was witnessed in this field, with platinum-based chemotherapy, therapy with checkpoint inhibitors, and more recently immunotherapy, all giving promising results (10). Although the role of radiotherapy is limited in the management of mUC patients in the context of improving survival, its addition to our therapeutic toolbox offers considerable symptomatic relief especially in patients with hematuria and bone metastases (11, 12).Our aim was to feature the role of radiotherapy (RT) in mUC, emphasizing the new RT techniques available and offer guidelines on how to apply this treatment modality in different clinical scenarios. To this end, the underlying molecular enigmas and quality of life (QoL) endpoints cannot be overlooked. To maximize patient benefit from RT, either as a monotherapy or alongside systemic therapy, we conclude that multi modal datasets need to be re-visited to better inform multicenter studies where polic...

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Section: Radiotherapy Combined With Novel Anticancer Agentsmentioning

confidence: 93%

Radiotherapy in Metastatic Urothelial Carcinoma: Rationale and Clinical Applications

et al. 2022

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“…To this day, there is still significant uncertainty regarding the best treatment course in platinum-refractory mUC patients pretreated with ICI. While the most reliable data are available for the antibody–drug conjugate enfortumab vedotin [ 15 ], there is a lack of knowledge in regard to other treatment options, highlighted in a recently published systemic review by Deiniger et al [ 12 ]. In Europe, also after the recent EMA-approval for enfortumab vedotin, vinflunine is still a standard of care after failure of sequential platinum-based chemotherapy and ICI treatment [ 2 , 16 ].…”

Section: Discussionmentioning

confidence: 99%

“…A real-world data analysis by Bamias et al showed superior efficacy with an overall response rate (ORR) of 18% and a tolerable safety profile of vinflunine in an unselected mUC population of 797 patients [ 10 ]. To date, little evidence exists about the use of vinflunine as a third-line agent after pretreatment with platinum-based chemotherapy and checkpoint inhibition [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of Vinflunine for Patients with Metastatic Urothelial Cancer after Immune Checkpoint Inhibitor Pretreatment—A Retrospective Multicenter Analysis

Riedel

Münker

Roghmann

et al. 2022

Cancers

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Background: Immune checkpoint inhibitors (ICI) are standard of care in patients with metastatic urothelial carcinoma (mUC) ineligible for cisplatin, and as second-line therapy after platinum-based chemotherapy. To date, few data exist about the efficacy of the former second-line chemotherapeutic agent vinflunine after the failure of sequential platinum-based chemotherapy and ICI treatment. The aim of this analysis was to examine the efficacy of vinflunine in a post-ICI third- or later-line setting. Methods: In this retrospective German multicenter study, data of mUC patients treated with vinflunine were reviewed in six centers between February 2010 and December 2021. All of the 105 included patients had radiologic progression after first-line platinum-based chemotherapy. The objective was to describe the efficacy of vinflunine in terms of overall response rate (ORR), clinical benefit rate (CBR), overall survival (OS), and progression-free survival (PFS) for post-ICI and ICI-naïve patients, respectively. Results: In our cohort, 61 patients (58.1%) had preceding immunotherapy before vinflunine administration, and 44 patients (41.9%) were ICI-naïve. Patients with ICI pretreatment showed an ORR of 22.4% compared to 15.6% within ICI-naïve patients (p = 0.451), and CBR was 51.0% vs. 25.0% (p = 0.020), respectively. Post-ICI patients showed longer OS (8.78 vs. 5.72 months; p = 0.467) and longer PFS (3.09 vs. 2.14 months; p = 0.105). Conclusion: This analysis supports the sequential use of vinflunine in post-ICI patients since the vinca-alkaloid retains a measurable clinical activity in these heavily pretreated patients. The therapeutic benefit may be higher than demonstrated in previous studies.

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“…NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count in the peripheral blood. The cutoff values for Hb, Alb, CRP, and NLR were derived from the area under the receiver operating characteristic (ROC) curve [22] and defined as the minimal values for (1 − sensitivity) 2 + (1 − specificity) 2 . In addition, the patients were divided into two groups according to the BOR: those who achieved CR or PR (responder group) or SD or PD (non-responder group).…”

Section: Patient Evaluationmentioning

confidence: 99%

“…Metastatic urothelial carcinoma (mUC) is an aggressive urological cancer, and the prognosis of patients with mUC remains poor, with a 5-year overall survival (OS) of only 4.6% [ 1 , 2 ]. Although platinum-based combination chemotherapy has been the first-line systemic treatment for mUC over the last two decades, the median OS has been reported to be 12–15 months [ 1 , 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

The Impact of Neutrophil-to-Lymphocyte Ratio after Two Courses of Pembrolizumab for Oncological Outcomes in Patients with Metastatic Urothelial Carcinoma

et al. 2022

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We focused on the therapeutic effect of pembrolizumab for metastatic urothelial carcinoma (mUC) and evaluated predictive factors for improving clinical outcomes. We conducted a retrospective multicenter cohort study of patients with mUC who received pembrolizumab. The endpoint was to evaluate the association between clinicopathological features and oncological outcomes. A total of 160 patients were enrolled in this study and were divided into two groups: the responder and the non-responder group, according to the best response. They were followed up for a median period of 10 months. The median overall (OS) and progression-free survival (PFS) in this study were 17 and 4 months, respectively. The responder group did not achieve median OS and it was 10 months in the non-responder group (p < 0.001). Similarly, the responder group did not achieve PFS, and it was 2 months in the non-responder group (p < 0.001). Regarding the neutrophil-to-lymphocyte ratio (NLR) after two courses of administration of pembrolizumab, patients with NLR < 3.24 had significantly better oncological outcomes than those with NLR ≥ 3.24. Multivariate analysis showed a significant association between NLR after two courses of pembrolizumab and OS. Therefore, the absolute value of NLR after two courses of pembrolizumab was a significant predictive factor for oncological outcomes.

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Current Systemic Treatment Options in Metastatic Urothelial Carcinoma after Progression on Checkpoint Inhibition Therapy—A Systemic Review Combined with Single-Group Meta-Analysis of Three Studies Testing Enfortumab Vedotin

Cited by 7 publications

References 78 publications

Radiotherapy in Metastatic Urothelial Carcinoma: Rationale and Clinical Applications

Radiotherapy in Metastatic Urothelial Carcinoma: Rationale and Clinical Applications

Efficacy of Vinflunine for Patients with Metastatic Urothelial Cancer after Immune Checkpoint Inhibitor Pretreatment—A Retrospective Multicenter Analysis

The Impact of Neutrophil-to-Lymphocyte Ratio after Two Courses of Pembrolizumab for Oncological Outcomes in Patients with Metastatic Urothelial Carcinoma

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