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Purpose This trial assessed the efficacy and safety of docetaxel monotherapy or docetaxel in combination with ramucirumab (vascular endothelial growth factor receptor 2 antibody) or icrucumab (vascular endothelial growth factor receptor 1 antibody) after progression during or within 12 months of platinum-based regimens for patients with locally advanced or metastatic urothelial carcinoma. Patients and Methods Patients were randomly assigned (1:1:1) to receive docetaxel 75 mg/m2 intravenously (IV) on day 1 of a 3-week cycle (arm A), docetaxel 75 mg/m2 IV plus ramucirumab 10 mg/kg IV on day 1 of a 3-week cycle (arm B), or docetaxel 75 mg/m2 IV on day 1 plus icrucumab 12 mg/kg IV on days 1 and 8 of a 3-week cycle (arm C). Treatment continued until disease progression or unacceptable toxicity. The primary end point was investigator-assessed progression-free survival (PFS). Results A total of 140 patients were randomly assigned and treated in arms A (n = 45), B (n = 46), or C (n = 49). PFS was significantly longer in arm B compared with arm A (median, 5.4 months; 95% CI, 3.1 to 6.9 months v 2.8 months; 95% CI, 1.9 to 3.6 months; stratified hazard ratio, 0.389; 95% CI, 0.235 to 0.643; P = .0002). Arm C did not experience improved PFS compared with arm A (1.6 months; 95% CI, 1.4 to 2.9; stratified hazard ratio, 0.863; 95% CI, 0.550 to 1.357; P = .5053). The most common grade 3 or worse adverse events (arms A, B, and C) were neutropenia (36%, 33%, and 39%), fatigue (13%, 30%, and 20%), febrile neutropenia (13%, 17%, and 6.1%), and anemia (6.7%, 13%, and 14%, respectively). Conclusion The addition of ramucirumab to docetaxel met the prespecified efficacy end point for prolonging PFS in patients with locally advanced or metastatic urothelial carcinoma receiving second-line treatment and warrants further investigation in the phase III setting.

Flex Tip Comparative AblationIntroductionNext‐generation catheters have been developed to reduce irrigation volume and preserve power delivery. A novel design uses a flexible tip (FlexAbility™ catheter) that directs flow to the contact surface. Because of recent safety issues with new catheters, we undertook a study in a canine heart with 3 irrigated catheters to compare efficacy and safety.MethodsEndocardial ablation was performed by 2 independent operators in 12 anesthetized canines with the FlexAbility (St. Jude Medical), ThermoCool™ (Biosense Webster), and ThermoCool™ SF (Biosense Webster) catheters. Endocardial RF lesions were delivered with each catheter in all 4 chambers of each animal for 52 ± 16 seconds. Each chamber was randomized to receive ablation from one catheter with recording of safety events. Cardiac pathology was performed with triphenyl tetrazolium chloride stain.ResultsAverage lesion dimensions were not significantly different between the 3 catheters. FlexAbility™ demonstrated a lower risk of steam pops relative to ThermoCool SF (P‐value = 0.013) despite equal mean power and radiofrequency time. High‐temperature generator shutdowns were observed with FlexAbility™ but not with either ThermoCool catheter. High‐temperature shutdowns were associated with larger average impedance drops (28.5 ohms vs. 19 ohms) without compromising lesion size.ConclusionsThe FlexAbility™ tip is safe and effective with no significant difference in lesion sizes compared to both standard ThermoCool and ThermoCool SF. FlexAbility™ has a significantly lower risk of steam pops compared to ThermoCool SF in a beating heart as defined predominantly by an abrupt rise of impedance.