Continuing Education
for Urology & GU Oncology Clinicians

Conference Coverage: ESMO 2019 Bladder

Barcelona, Spain (UroToday.com) Platinum-based chemotherapy has been the standard first-line therapy for patients with metastatic urothelial cancer (mUC). Historically, response to standard of care second-line chemotherapy regimens is < 15%. Although immune checkpoint inhibitors (ICIs) now provide another option for patients with platinum-refractory mUC, response rates are similarly low, highlighting a critical need for novel therapeutic agents in this disease setting. Dr. Scott Tagawa presents the initial results from TROPHY-U-01: A Phase 2 open-label study of Sacituzumab Govitecan (SG) in patients with mUC after progression on platinum-based chemotherapy or an ICI.

Non-Accredited

Barcelona, Spain (UroToday.com) Stage III (cT3-4aN0M0 or ≥cT1N+M0) urothelial cancer patients have a poor prognosis, and despite high response rates, pre-operative chemotherapy shows limited survival benefit. Furthermore, the overall survival benefit of preoperative cisplatin-based chemotherapy is only 5%, with 30-40% being cisplatin ineligible. Immunotherapy targeting PD-1/PD-L1 is active in metastatic urothelial carcinoma and the combination of ipilimumab and nivolumab appears to increase response rates. Encouraging pathological complete response (pCR) rates (29-42%) have been observed in trials testing neoadjuvant anti-PD-1/PD-L1, however these have been mostly cT2-T3N0 patients. At the ESMO 2019 annual congress, Dr. Van der Heijden and colleagues presented initial findings assessing preoperative ipilimumab + nivolumab in patients with locally advanced urothelial cancer.

Non-Accredited

Barcelona, Spain (UroToday.com) Cisplatin based chemotherapy has been the standard of care first line therapy for metastatic urothelial carcinoma (mUC) for several decades. However, up to 50% of patients may not be medically eligible for cisplatin chemotherapy, and so efficacious alternative first line regimens are required. Based on phase 2 data, the FDA has approved both pembrolizumab (anti-PD1) and atezolizumab (anti-PDL1) as first line therapies for mUC based on phase II data showing efficacy and durable response from the KEYNOTE052 and IMvigor 210 trials, though long term outcomes have not yet been reported for these trials. The impact of first line combination immunotherapy and chemotherapy on patient outcomes in mUC has not been tested.

Non-Accredited

Barcelona, Spain (UroToday.com) Atezolizumab has received regulatory approval for patients with locally advanced or metastatic urothelial carcinoma.  This has occurred for both cisplatin-ineligible patients in the first-line setting and also for those in the post-platinum treated setting.1, 2  In other malignancies, such as lung cancer, major advances have been made in treatment outcomes when cytotoxic chemotherapy has been combined with up front checkpoint inhibition with immune-oncology (IO) agents.  Hence, multiple efforts have been launched with combination chemotherapy and atezolizumab, an anti-PD-L1 antibody as well as pembrolizumab, an anti-PD-1 antibody, in the first-line metastatic urothelial carcinoma setting.

Non-Accredited

Barcelona, Spain (UroToday.com) Platinum-based chemotherapy remains the standard of care for patients with locally advanced or metastatic urothelial carcinoma. Despite the use of first-line PD-1/PD-1L inhibitors, 71–76% of patients who are cisplatin-ineligible do not respond to treatment. Enfortumab vedotin is an antibody-drug conjugate targeting Nectin-4, which is highly expressed in metastatic urothelial carcinoma. Enfortumab vedotin monotherapy data are encouraging, initially presented at ASCO 2019, demonstrating a 44% response rate (12% complete response). Perhaps combination therapy may provide additional benefit – the working hypothesis is that combination enfortumab vedotin plus pembrolizumab is feasible, safe, and may lead to improved responses compared to historical controls in the first-line cisplatin-ineligible setting. At the 2019 European Society for Medical Oncology annual meeting (ESMO) proffered paper session, Dr. Hoimes and colleagues presented initial data on a cohort of cisplatin-ineligible patients receiving first line enfortumab vedotin + pembrolizumab.

Non-Accredited