Adding bevacizumab to gemcitabine plus cisplatin (GC) did not improve overall survival (OS) in patients with metastatic urothelial carcinoma, according to a study published in the Journal of Clinical Oncology.

Angiogenesis has been linked to the growth and progression of urothelial cancer, and vascular endothelial growth factor A (VEGF-A) is thought to be the primary driver of angiogenesis in urothelial carcinoma.

Therefore, researchers sought to determine if angiogenesis inhibition with bevacizumab, a humanized anti-VEGF-A antibody, would improve survival in patients with metastatic urothelial cancer. 

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The researchers conducted the randomized, double-blind, phase 3 CALGB 90601 (Alliance) trial ( Identifier: NCT00942331) to test their theory.

The study enrolled 506 patients with metastatic urothelial carcinoma who had not received prior chemotherapy for metastatic disease and had not received neoadjuvant or adjuvant chemotherapy within 12 months.

The patients were randomly assigned to receive either GC plus bevacizumab (252 patients) or GC plus placebo (254 patients).

The primary endpoint was OS. The secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and toxicity.

At a median follow-up of 76.3 months, the median OS was 14.5 months in the bevacizumab arm and 14.3 months in the placebo arm (hazard ratio [HR], 0.87; 95% CI, 0.72-1.05; P =.15). 

The median PFS was significantly longer in the bevacizumab arm than in the placebo arm — 8 months and 6.7 months, respectively (HR, 0.77; 95% CI, 0.63-0.95; P =.015) — but this difference was not considered clinically meaningful.

There was no significant difference in the ORR between the 2 arms. The confirmed ORR was 40.4% in the bevacizumab arm and 36.4% in the placebo arm (P =.56).

The overall incidence of grade 3 or higher adverse events (AEs) did not differ significantly between the arms.

Serious AEs occurred in 84 patients (35.4%) in the bevacizumab arm and in 73 patients (31.5%) in the placebo arm.

AEs that were more frequent in the bevacizumab arm included hypertension (24% vs 6%) and proteinuria (10% vs 3%).

“Data from recent phase 3 trials show that platinum-based chemotherapy remains the standard of care for most patients, followed by immunotherapy either as maintenance for patients with a response or stable disease or as treatment for disease progression on platinum-based chemotherapy,” the study authors wrote. “Further work is needed to identify those patients where angiogenesis inhibition might be critical.”

Disclosures: This research was supported by Genentech, the National Cancer Institute, and others. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Rosenberg JE, Ballman KA, Halabi S, et al. 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. Published online May 14, 2021. doi:10.1200/JCO.21.00286