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ESMO 2018 Bladder Cancer

ESMO 2018: ABACUS, A phase II Study Investigating the Safety and Efficacy of Neoadjuvant Atezolizumab in Muscle Invasive Bladder Cancer

Munich, Germany ( UroToday.com) There is a high metastatic relapse rate for patients with muscle-invasive bladder cancer after cystectomy – neoadjuvant chemotherapy can decrease that risk. The standard of care neoadjuvant therapy for muscle-invasive bladder cancer typically involves a cisplatin-based regimen, the most common being MVAC (methotrexate, vinblastine, doxorubicin, cisplatin), GC (gemcitabine and cisplatin), or CMV (cisplatin, vinblastine, and methotrexate).  Compared with cystectomy alone, neoadjuvant chemotherapy can improve overall survival and decrease the risk of recurrence1,2

ESMO 2018: Overall Survival Results – RANGE, Ramucirumab and Docetaxel In Platinum-Refractory Urothelial Carcinoma

Munich, Germany (UroToday.com) Ramucirumab is a monoclonal antibody directed against vascular endothelial growth factor receptor 2 (VEGFR2). VEGFR1 and 2 and their ligands are critical for tumor angiogenesis and are thought to contribute to the progression of urothelial carcinoma1. An interesting study by Crew et al measured urinary VEGF and found that urinary VEGF correlated with UC recurrence1.

ESMO 2018: Comprehensive Biomarker Analyses and Updated Results of PURE-01 Study: Neoadjuvant Pembrolizumab in Muscle-Invasive Urothelial Bladder Carcinoma

Munich, German (UroToday.com) The PURE-01 study is an assessment of pembrolizumab (immune checkpoint inhibitor) in the neoadjuvant setting for muscle-invasive bladder cancer (MIBC). It is a single-arm, phase 2 study of Pembro preceding radical cystectomy in MIBC. In this presentation, the authors present updated results and results of their correlative biomarker analysis. 

ESMO 2018: Is There Still a Role for Chemotherapy in Bladder Cancer?

Munich, Germany (UroToday.com) Maria De Santis, MD, gave an overview of the role of chemotherapy in bladder cancer patients. Chemotherapy for bladder cancer began in the 1980s with the discovery of the methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) protocol.1 M-VAC was later upgraded to a high dose (HD), dose-dense (DD)2 or accelerated dose (AMVAC).3 The newer option is Gemcitabine and cisplatin (GC), which has similar efficacy to MVAC but with improved toxicity profile in the metastatic setting.4 Later, GC was upgraded to GC split dose.5

ESMO 2018: Neoadjuvant Therapy with Pembrolizumab Alone or in Combination with Cisplatin plus Gemcitabine for Locally Advanced Urothelial Cancer, A Phase Ib/2 Study

Munich, Germany (UroToday.com) Treatment of muscle-invasive urothelial cancer can involve a combination of systemic therapies, radiation, and surgery. When muscle-invasive urothelial cancer (UC) is treated with surgery alone, almost half of patients will develop metastatic disease within two years, and 5-year survival overall survival for patients who receive only cystectomy or radiation range from 27% - 88%1.

ESMO 2018: RANGE, A Phase 3, Randomized, Placebo-Controlled, Double-Blind Trial of Ramucirumab and Docetaxel In Platinum-Refractory Urothelial Carcinoma: Overall Survival Results

Munich, Germany (UroToday.com) Until the introduction and, ultimately, approval of multiple immune checkpoint inhibitors in the setting of platinum-refractory metastatic urothelial carcinoma (mUC), docetaxel was the standard of care 2nd line therapy. However, at the time of initiation of the RANGE study, ICI’s had not yet been introduced nor had they been approved.

ESMO 2018: A Phase Ib/2 Study of Neoadjuvant Pembrolizumab and Chemotherapy for Locally Advanced Urothelial Cancer

Munich, Germany (UroToday.com) Neoadjuvant chemotherapy for muscle-invasive bladder cancer is an established treatment paradigm supported by Level 1 evidence. Historically utilizing an MVAC regimen, there was subsequently a shift to Gem-Cis and, more recently dose-dense MVAC (ddMVAC). Indeed, these studies have repeatedly demonstrated good tolerability with the dose-dense regimens. Meta-analyses put the increased survival benefit at 5-7%, if all comers are treated. However, the greatest benefit is in the population of patients with complete response (pT0) at the time of cystectomy; however, even patients with residual non-muscle-invasive (<pT2 disease) do better than patients not receiving chemotherapy.
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