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

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).

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.

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.

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.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2021 May 14 [Epub ahead of print]

Jonathan E Rosenberg, Karla A Ballman, Susan Halabi, Pamela J Atherton, Amir Mortazavi, Christopher Sweeney, Walter M Stadler, Benjamin A Teply, Joel Picus, Scott T Tagawa, Sreedhar Katragadda, Daniel Vaena, Jamal Misleh, Christopher Hoimes, Elizabeth R Plimack, Thomas W Flaig, Robert Dreicer, Dean Bajorin, Olwen Hahn, Eric J Small, Michael J Morris

Memorial Sloan Kettering Cancer Center, New York, NY., Alliance Statistics and Data Center, Weill Medical College of Cornell University, New York, NY., Alliance Statistics and Data Center, Duke University, Durham, NC., Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN., Division of Medical Oncology, Department of Internal Medicine, College of Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH., Dana-Faber Cancer Institute, Harvard Medical School, Boston, MA., University of Chicago Comprehensive Cancer Center, Chicago, IL., University of Nebraska Medical Center, Omaha, NE., Washington University School of Medicine, St Louis, MO., Weill Cornell Medical College, New York, NY., Cone Health Cancer Center, Greensboro, NC., University of Iowa/Holden Comprehensive Cancer Center, Iowa City, IA., Christiana Care NCI Community Oncology Research Program, Newark, DE., Case Comprehensive Cancer Center at UH-Seidman, Cleveland, OH., Fox Chase Cancer Center, Philadelphia, PA., University of Colorado Denver School of Medicine, Aurora, CO., University of Virginia Cancer Center, Charlottesville, VA., University of California San Francisco Comprehensive Cancer Center, San Francisco, CA.

Read an Expert Commentary by Bishoy Faltas, MD