Pazopanib plus paclitaxel may increase survival in refractory urothelial cancer

The combination of pazopanib and paclitaxel induced higher response rates and extended survival compared with other second-line regimens for relapsed or refractory urothelial cancer, according to results of a phase 2 trial.

An estimated 74,000 new cases of metastatic urothelial cancer occurred in the United States last year, and about 16,000 people died of the disease.

Patients with urothelial cancer treated with platinum-based chemotherapy achieve a median PFS of about 8 months, and 5-year OS is about 15%. Therefore, most patients require additional therapy, but no standard exists.

The combination of the tyrosine kinase inhibitor pazopanib (Votrient, Novartis) with weekly paclitaxel conferred favorable outcomes in a phase 1 trial of patients with advanced solid tumors.

Sujata Narayanan, MD, medical oncologist at Stanford Cancer Institute, and colleagues conducted a phase 2 study to evaluate the combination in 28 patients with refractory urothelial cancer.

All patients had refractory urothelial cancer and demonstrated disease progression after two prior chemotherapeutic regimens.

Patients received a median four cycles of 80 mg/m² paclitaxel on days 1, 8 and 15 of each 28-day cycle, as well as 800 mg oral pazopanib daily.

Overall response rate served as the primary endpoint. Secondary endpoints included PFS, OS and safety.

Three patients achieved complete response and 12 patients achieved partial response, equating to an ORR of 54% (95% CI, 33.9-72.5). Eleven patients achieved stable disease and two patients experienced progressive disease.

Researchers reported median PFS of 6.2 months (95% CI, 5.6-7.7) and median OS of 10 months (95% CI, 5.7-16).

The response rate and median survival exceeded those observed with existing second-line regimens, Narayanan and colleagues wrote.

The most frequent side effects were fatigue (63%), diarrhea (44%), nausea/vomiting (41%) and neuropathy (24%). Hematological toxicities also were common. They included anemia (69%), thrombocytopenia (47%) and neutropenia (38%).

The researchers acknowledged potential limitations to their study, including the small sample size and possible selection bias.

Narayanan and colleagues recommended that a phase 3 trial be conducted to compare the combination with single-agent paclitaxel.

“While new immunotherapies, such as PD-1 blockade, are very promising, a subset does not respond to this approach,” they wrote. “Thus, tolerable combinations with other mechanisms of action and promising efficacy, such as paclitaxel-pazopanib, merit a larger study with incorporation of patients stratified based on their performance status, hemoglobin, visceral metastasis and time from prior chemotherapy.” – by Kristie L. Kahl

Disclosure: The researchers report no relevant financial disclosures.