In a phase II trial reported in JAMA Oncology, Srikala S. Sridhar, MD, MSc, FRCPC, and colleagues found no difference in progression-free survival with nab-paclitaxel vs paclitaxel in patients with platinum-refractory metastatic urothelial cancer.
Srikala S. Sridhar, MD, MSc, FRCPC
Study Details
In the investigator-initiated open-label trial, 199 patients from sites in Canada and Australia were randomly assigned between January 2014 and April 2017 to receive nab-paclitaxel at 260 mg/m2 (n = 99) or paclitaxel at 175 mg/m2 (n = 100) every 3 weeks. Patients with mixed histologic findings (except small cell) were eligible so long as urothelial cancer was the predominant histologic finding.
All patients had received platinum-based chemotherapy in the metastatic setting or were within 12 months of perioperative chemotherapy. Patients with prior taxane therapy were excluded from the study. The primary endpoint was progression-free survival.
Progression-Free Survival
Median follow-up was 16.4 months. Median progression-free survival was 3.4 months in the nab-paclitaxel group vs 3.0 months in the paclitaxel group (hazard ratio [HR] = 0.92, 90% confidence interval [CI] = 0.68–1.23; P = .31).
Treatments after disease progression consisted of chemotherapy in nine patients in the nab-paclitaxel group and six in the paclitaxel group, and immunotherapy in six patients in each group. Median overall survival was 7.5 months in the nab-paclitaxel group vs 8.8 months in the paclitaxel group (HR = 0.95, 90% CI = 0.70–1.30; P = .40).
Objective response rates were 22% (including complete response in 3 patients) in the nab-paclitaxel group vs 25% (including complete response in 2 patients) in the paclitaxel group (P = .97). Median duration of response was 4.4 months vs 4.3 months.
KEY POINTS
- No difference in progression-free survival was observed with nab-paclitaxel vs paclitaxel.
- Nab-paclitaxel was associated with a higher rate of grade ≥ 3 adverse events.
Adverse Events
Grade ≥ 3 adverse events occurred in 66% of patients in the nab-paclitaxel group vs 46% of the paclitaxel group (P = .009). Peripheral sensory neuropathy of any grade occurred in 74% vs 66% and was grade 3 or 4 in 7% vs 3% (P = .27). The most common nonhematologic grade ≥ 3 adverse events occurring in ≥ 5% of patients were fatigue (15%) and peripheral sensory neuropathy in the nab-paclitaxel group and fatigue (12%) in the paclitaxel group. Grade ≥ 3 neutropenia occurred in 13% vs 7% of patients; rates of grade ≥ 3 anemia and thrombocytopenia were < 10% in each group. One treatment-related death was observed (due to gastric perforation in a patient in the paclitaxel group).
No apparent differences in health-related quality of life were observed.
The investigators concluded, “In this open-label, phase II randomized clinical trial of patients with platinum-refractory metastatic urothelial cancer, nab-paclitaxel had similar efficacy to paclitaxel; but worse toxic effects. The objective response rate with either taxane, however, was higher than previously reported and similar to those reported for the immune checkpoint inhibitors, suggesting that the taxanes remain a reasonable option in this setting.”
Dr. Sridhar, of the Princess Margaret Cancer Centre, University of Toronto, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by Celgene and Specialised Therapeutics. For full disclosures of the study authors, visit jamanetwork.com.
