Despite research efforts, an effective salvage treatment for metastatic urothelial cancer that has relapsed following first-line chemotherapy for metastatic disease remains an unmet need. Three different abstracts presented at the recent Genitourinary Cancers Symposium evaluated therapies in this setting. A randomized phase II study was negative for the addition of vandetanib to docetaxel in patients with advanced urothelial cancer. Two separate phase II studies had reported favorable results for single-agent nab-paclitaxel (Abraxane) and cetuximab (Erbitux) plus paclitaxel, respectively, in this setting, although both studies were small and not definitive. At best, “cautious optimism” is the watchword regarding these two strategies. Both require further study.

Vandetanib plus Docetaxel

In a multi-institutional, double-blind, randomized phase II trial in 142 patients with previously treated, platinum-resistant advanced urothelial cancer, the addition of the investigational agent vandetanib to docetaxel failed to improve progression-free survival, overall response rate, or overall survival and incurred greater toxicity compared with docetaxel alone.¹

A total of 37 patients whose disease progressed on the docetaxel arm crossed over to vandetanib. Vandetanib had no benefit in these patients.

“There is no standard of care for metastatic urothelial cancer that progresses after platinum-containing chemotherapy. The study sought to evaluate whether the addition of vandetanib, a dual antiangiogenesis inhibitor which blocks VEGF and EGFR simultaneously, would provide added benefit to docetaxel. The study was negative, and new treatments are urgently needed,” stated lead author Toni Choueiri, MD, Dana-Farber Cancer Institute, Boston.

Single-agent Nab-paclitaxel

A phase II trial evaluated single-agent nab-paclitaxel, the albumin-bound nanoparticle formulation of paclitaxel, in 48 patients with urothelial cancer that progressed on or after platinum-based first-line chemotherapy.² Among 47 patients evaluable for response, partial responses were achieved in 15 patients (32%) and stable disease in 10 (21%); 22 patients (47%) had progressive disease.

Thus, the clinical benefit rate (response or stable disease) was 53%, reported Srikala S. Sridhar, MD, Princess Margaret Hospital, Toronto. “This is the highest reported single-agent response rate to date in the second-line setting for urothelial cancer, and further study is clearly warranted,” she concluded.

Cetuximab plus Paclitaxel

A multicenter, randomized, phase II study of 39 evaluable patients with metastatic urothelial cancer previously treated with one line of chemotherapy suggests that cetuximab augments the antitumor activity of paclitaxel in this setting.³ This combination requires further study to establish its role in the treatment of urothelial cancer, said lead author Yu-Ning Wong, MD, Fox Chase Cancer Center, Philadelphia.

The two-armed study was noncomparative. The goal was to study the effect of cetuximab with or without paclitaxel in this setting. The investigators decided to close the cetuximab-alone arm after 9 of the first 11 patients showed disease progression by 8 weeks. A total of 28 patients completed accrual to the cetuximab/paclitaxel arm. Median progression-free survival of the combination arm was 115 days (16.4 weeks) overall. The overall survival was 9.5 months. The overall response rate of the combination arm was 28.5% (eight patients had a complete or partial response); unconfirmed partial responses were seen in an additional four patients. ■

Financial Disclosure: Dr. Choueiri received research funding for his study from AstraZeneca. Dr. Sridhar disclosed financial ties to Sanofi-aventis and Pfizer. Dr. Wong received funding for this study from Bristol-Myers Squibb. She has also served as a paid and unpaid consultant to Bristol-Myers Squibb.

References

1. Choueiri TK, Vaishampayan UN, Yu EY, et al: A double-blind, randomized trial of docetaxel plus vandetanib versus docetaxel plus placebo in platinum-pretreated advanced urothelial cancer. Genitourinary Cancers Symposium. Abstract LBA239. Presented February 18, 2011,

2. Sridhar SS, Canil CM, Mukherjee SM, et al: Results of a phase II study of single-agent nab-paclitaxel in platinum-refractory second-line metastatic urothelial carcinoma. Genitourinary Cancers Symposium. Abstract 241. Presented February 18, 2011.

3. Wong YN, Litwin S, Plimack ER, et al: Effect of EGFR inhibition with cetuximab on the efficacy of paclitaxel in previously treated metastatic urothelial cancer. Genitourinary Cancers Symposium. Abstract 243. Presented February 18, 2011.