Randomized Phase III Trial of Gemcitabine and Cisplatin With Bevacizumab or Placebo in Patients With Advanced Urothelial Carcinoma: Results of CALGB 90601 (Alliance)

J Clin Oncol. 2021 Aug 1;39(22):2486-2496. doi: 10.1200/JCO.21.00286. Epub 2021 May 14.


Purpose: The combination of gemcitabine and cisplatin (GC) is a standard therapy for metastatic urothelial carcinoma. Based on data that angiogenesis plays a role in urothelial carcinoma growth and progression, a randomized placebo-controlled trial was performed with the primary objective of testing whether patients treated with GC and bevacizumab (GCB) have superior overall survival (OS) than patients treated with GC and placebo (GCP).

Patients and methods: Between July 2009 and December 2014, 506 patients with metastatic urothelial carcinoma without prior chemotherapy for metastatic disease and no neoadjuvant or adjuvant chemotherapy within 12 months were randomly assigned to receive either GCB or GCP. The primary end point was OS, with secondary end points of progression-free survival, objective response, and toxicity.

Results: With a median follow-up of 76.3 months among alive patients, the median OS was 14.5 months for patients treated with GCB and 14.3 months for patients treated with GCP (hazard ratio for death = 0.87; 95% CI, 0.72 to 1.05; two-sided stratified log-rank P = .14). The median progression-free survival was 8.0 months for GCB and 6.7 months for GCP (hazard ratio = 0.77; 95% CI, 0.63 to 0.95; P = .016). The proportion of patients with grade 3 or greater adverse events did not differ significantly between both arms, although increased bevacizumab-related toxicities such as hypertension and proteinuria occurred in the bevacizumab-treated arm.

Conclusion: The addition of bevacizumab to GC did not result in improved OS. The observed median OS of about 14 months is consistent with prior phase III trials of cisplatin-based chemotherapy.

Trial registration: ClinicalTrials.gov NCT00942331.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiogenesis Inhibitors / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab / administration & dosage
  • Cisplatin / administration & dosage
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Double-Blind Method
  • Female
  • Gemcitabine
  • Humans
  • Male
  • Neovascularization, Pathologic / drug therapy
  • Survival Analysis
  • Urinary Bladder Neoplasms / blood supply
  • Urinary Bladder Neoplasms / drug therapy
  • Urologic Neoplasms / blood supply
  • Urologic Neoplasms / drug therapy*


  • Angiogenesis Inhibitors
  • Deoxycytidine
  • Bevacizumab
  • Cisplatin
  • Gemcitabine

Associated data

  • ClinicalTrials.gov/NCT00942331