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Docetaxel As Monotherapy or Combined With Ramucirumab or Icrucumab in Second-Line Treatment for Locally Advanced or Metastatic Urothelial Carcinoma: An Open-Label, Three-Arm, Randomized Controlled Phase II Trial

2016; Lippincott Williams & Wilkins; Volume: 34; Issue: 13 Linguagem: Inglês

10.1200/jco.2015.65.0218

1527-7755

Daniel P. Petrylak, Scott T. Tagawa, Manish Kohli, Andrea Eisen, Christina Canil, Srikala S. Sridhar, Alexander I. Spira, Evan Y. Yu, John M. Burke, David R. Shaffer, Chong‐Xian Pan, Jenny J. Kim, Jeanny B. Aragon‐Ching, David I. Quinn, Nicholas J. Vogelzang, Shande Tang, Hui Zhang, Christopher Cavanaugh, Ling Gao, John S. Kauh, Richard A. Walgren, Kim N.,

Gastric Cancer Management and Outcomes

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/m 2 intravenously (IV) on day 1 of a 3-week cycle (arm A), docetaxel 75 mg/m 2 IV plus ramucirumab 10 mg/kg IV on day 1 of a 3-week cycle (arm B), or docetaxel 75 mg/m 2 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.