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available at http://www.ncbi.nlm.nih.gov/pubmed/28916371 Editorial Comment: Increasing attention has been placed on the treatment of advanced or metastatic urothelial carcinoma that has progressed during or after platinum based chemotherapy. Inroads have been made with immunotherapy options, with multiple new drugs (eg atezolizumab and pembrolizumab) approved in this setting. This study examined the safety and efficacy of a VEGFR-2 antagonist, ramucirumab, plus docetaxel vs placebo plus docetaxel in a randomized, double-blind, 1052 BLADDER, PENIS AND URETHRAL CANCER, AND BASIC PRINCIPLES OF ONCOLOGY Copyright © 2019 American Urological Association Education and Research, Inc. Unauthorized reproduction of this article is prohibited. phase 3 trial. A total of 530 patients were randomized 1:1 to these regimens between July 2015 and April 2017, and the primary end point was progression-free survival. There was a statistically significant lengthening of progression-free survival from 2.76 months to 4.07 months (HR 0.757, p [ 0.0118). An objective response was seen in 24.5% of patients receiving ramucirumab. However, more than 60% of patients in both arms had grade 3 or worse adverse events. This trial revealed a benefit in progression-free survival but overall survival advantage data are unavailable. It remains unclear what the clinical benefit of this statistical difference of slightly more than 1 month means. These data show this VEGFR-2 antagonist as the first in class agent to demonstrate a positive treatment effect for advanced urothelial carcinoma. More mature data will allow a better understanding of how this regimen will fit into the treatment algorithm. Sam S. Chang, MD Suggested Reading Siefker-Radtke AO, Apolo AB, Bivalacqua TJ et al: Immunotherapy with checkpoint blockade in the treatment of urothelial carcinoma. J Urol 2018; 199: 1129. Oing C, Rink M, Oechsle K et al: Second line chemotherapy for advanced and metastatic urothelial carcinoma: vinflunine and beyondda comprehensive review of the current literature. J Urol 2016; 195: 254. Re: Safety and Efficacy of Temsirolimus as Second Line Treatment for Patients with Recurrent Bladder Cancer M. Pulido, G. Roubaud, A. L. Cazeau, H. Mahammedi, L. Vedrine, F. Joly, L. Mourey, C. Pfister, A. Goberna, B. Lortal, C. Bellera, P. Pourquier and N. Hou ed e Clinical and Epidemiology Department, Clinical Investigation Center INSERM CIC 1401, and Medical Oncology and Nuclear Medicine Departments, Bergoni e Institute, Bordeaux, Urology Department, Rouen University Hospital and Clinical Investigation Center INSERM CIC 1404, Rouen, Medical Oncology Department, Jean Perrin Cancer Center, Clermont-Ferrand, Hartmann Oncology Radiotherapy Group, Levallois-Peret, Medical Oncology Department, François Baclesse Cancer Center, Caen, Medical Oncology Department, IUCT Oncopole, Toulouse, INSERM U1194, Montpellier Cancer Research Institute, Montpellier and Medical Oncology Department, Nimes University Hospital, Nimes, France BMC Cancer 2018; 18: 194. doi: 10.1186/s12885-018-4059-5 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/29454321available at http://www.ncbi.nlm.nih.gov/pubmed/29454321 Editorial Comment: This single arm, phase 2 trial examined the mTOR inhibitor temsirolimus in 54 patients with relapsed bladder cancer after first line chemotherapy. The primary objective was to determine the efficacy of 2-month nonprogression based on RECIST (Response Evaluation Criteria in Solid Tumors). This trial accrued patients from November 2009 to July 2014, of whom 48.9% met criteria of nonprogression at the 2-month mark, with the majority having stable disease. A small subset (9% of patients) was treated for more than 30 months, thus showing that a small cohort can have long-standing response. However, 52.8% had grade 3 to 4 adverse events and more than 20% had to stop treatment due to toxicity. As the authors state, any enthusiasm for further evaluation of temsirolimus must be tempered by the significant side effect profile. In addition, not enough data exist to predict who is most likely to benefit from administration. During the time it took to accrue patients for this trial immunotherapeutic breakthroughs may have pushed this treatment option further back in the queue of options as well as choices for future study. Sam S. Chang, MD Suggested Reading Siefker-Radtke AO, Apolo AB, Bivalacqua TJ et al: Immunotherapy with checkpoint blockade in the treatment of urothelial carcinoma. J Urol 2018; 199: 1129. Oing C, Rink M, Oechsle K et al: Second line chemotherapy for advanced and metastatic urothelial carcinoma: vinflunine and beyondda comprehensive review of the current literature. J Urol 2016; 195: 254. Lerner SP: Targeted therapies for metastatic bladder cancer. J Urol 2015; 193: 8. BLADDER, PENIS AND URETHRAL CANCER, AND BASIC PRINCIPLES OF ONCOLOGY 1053 Copyright © 2019 American Urological Association Education and Research, Inc. Unauthorized reproduction of this article is prohibited.