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J Clin Oncol. 2016 May 1;34(13):1500-9. doi: 10.1200/JCO.2015.65.0218. Epub 2016 Feb 29.

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.

Author information

1
Daniel P. Petrylak, Yale University Cancer Center, New Haven, CT; Scott T. Tagawa, Weill Cornell Medical College, New York; David Shaffer, New York Oncology Hematology, Albany, NY; Manish Kohli, Mayo Clinic, Rochester, MN; Andrea Eisen, Sunnybrook Health Sciences Centre; Srikala S. Sridhar, Princess Margaret Hospital, Toronto; Christina Canil, Ottawa Hospital Cancer Centre, Ottawa, Ontario; Kim N. Chi, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Alexander Spira, Virginia Cancer Specialists, Fairfax, VA; Alexander Spira, John M. Burke, David Shaffer, and Nicholas J. Vogelzang, US Oncology Research, The Woodlands, TX; Evan Y. Yu, University of Washington Medical Center and Fred Hutchinson Cancer Research Center, Seattle, WA; John M. Burke, Rocky Mountain Cancer Centers, Aurora, CO; Chong-Xian Pan, University of California-Davis Medical Center, Sacramento; David I. Quinn, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA; Jenny J. Kim, Johns Hopkins University, Baltimore, MD; Jeanny B. Aragon-Ching, George Washington University Medical Center, Washington, DC; Nicholas J. Vogelzang, Comprehensive Cancer Centers of Nevada, Las Vegas, NV; Shande Tang, Hui Zhang, Christopher T. Cavanaugh, Ling Gao, and John S. Kauh, Eli Lilly, Bridgewater, NJ; and Richard A. Walgren, Eli Lilly, Indianapolis, IN. daniel.petrylak@yale.edu.
2
Daniel P. Petrylak, Yale University Cancer Center, New Haven, CT; Scott T. Tagawa, Weill Cornell Medical College, New York; David Shaffer, New York Oncology Hematology, Albany, NY; Manish Kohli, Mayo Clinic, Rochester, MN; Andrea Eisen, Sunnybrook Health Sciences Centre; Srikala S. Sridhar, Princess Margaret Hospital, Toronto; Christina Canil, Ottawa Hospital Cancer Centre, Ottawa, Ontario; Kim N. Chi, British Columbia Cancer Agency, Vancouver, British Columbia, Canada; Alexander Spira, Virginia Cancer Specialists, Fairfax, VA; Alexander Spira, John M. Burke, David Shaffer, and Nicholas J. Vogelzang, US Oncology Research, The Woodlands, TX; Evan Y. Yu, University of Washington Medical Center and Fred Hutchinson Cancer Research Center, Seattle, WA; John M. Burke, Rocky Mountain Cancer Centers, Aurora, CO; Chong-Xian Pan, University of California-Davis Medical Center, Sacramento; David I. Quinn, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA; Jenny J. Kim, Johns Hopkins University, Baltimore, MD; Jeanny B. Aragon-Ching, George Washington University Medical Center, Washington, DC; Nicholas J. Vogelzang, Comprehensive Cancer Centers of Nevada, Las Vegas, NV; Shande Tang, Hui Zhang, Christopher T. Cavanaugh, Ling Gao, and John S. Kauh, Eli Lilly, Bridgewater, NJ; and Richard A. Walgren, Eli Lilly, Indianapolis, IN.

Abstract

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01282463.

PMID:
26926681
DOI:
10.1200/JCO.2015.65.0218
[Indexed for MEDLINE]

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