Vinflunine plus best supportive care improved survival in advanced urothelial cancer

Results from a European study demonstrate the efficacy of vinflunine plus best supportive care in the second-line setting.

Compared with best supportive care alone, vinflunine — a novel microtubule inhibitor — plus best supportive care as second-line therapy reduced the risk for death by 23% in patients with advanced transitional cell urothelial cancer, according to data from a phase-3 trial published in The Journal of Clinical Oncology.

Conducted in Europe where transitional cell urothelial cancer accounts for about 7% of all human neoplasms, the trial was based on results of two previous phase-2 trials demonstrating vinflunine’s efficacy in terms of response rate and long-duration responses.

The randomized, multinational study included 370 patients with advanced transitional cell urothelial cancer who progressed after a first-line platinum-containing regimen. Patients were randomly assigned to vinflunine plus best supportive care (n=253) or best supportive care alone (n=117).

Patients with a performance status of zero were assigned to 320 mg/m² vinflunine every three weeks; those with a performance status of zero and previous pelvic radiation and those with a performance status of one were assigned to 280 mg/m² vinflunine, which was escalated to 320 mg/m². The primary endpoint was OS; secondary endpoints included overall response rate, control rate and duration and PFS.

Combination increased survival

Though not statistically significant, researchers reported a two-month survival benefit from vinflunine plus best supportive care in the intent-to-treat population (6.9 months vs. 4.6 months; HR=0.88; 95% CI, 0.69-1.12). Results of a multivariate Cox analysis that adjusted for prognostic factors demonstrated a statistically significant benefit to OS in the vinflunine plus best supportive care group (P=.036), yielding a 23% reduction in the risk for death (95% CI, 0.61-0.98).

An analysis of patients eligible for demonstrating statistical significance (n=357) demonstrated an improvement in OS in the vinflunine plus best supportive care group compared with best supportive care alone (6.9 months vs. 4.3 months; P=.040).

Vinflunine plus best supportive care was also associated with superior overall response rate (P=.006), disease control (P=.002) and PFS (P=.001).

According to Robert Dreicer, MD, department of solid tumor oncology at the Taussig Cancer Institute at the Cleveland Clinic, and the author of an accompanying editorial, many clinicians still offer patients cytotoxic therapy to improve or delay symptoms associated with transitional cell urothelial cancer, reserving best supportive care for unfit patients.

These results, he wrote, “may be interpreted as providing justification for this approach, and many clinicians will infer (as is the case with primary therapy for metastatic disease) that other antineoplastic agents with similar objective activity (from phase-2 salvage studies) in advanced urothelial cancer are likely to provide similar clinical benefit.”

According to the researchers, neutropenia occurred in half of patients assigned to vinflunine plus best supportive care; however, the toxicity was reversible and caused only two patients to discontinue treatment. Other common grade-3 and -4 toxicities in the combination arm included febrile neutropenia (6%), anemia (19%), fatigue (19%) and constipation (16%).

Using the EORTC Quality of Life Questionnaire, researchers assessed quality of life on days 21, 42, 84 and 126 in both groups. According to the results, compared with best supportive care alone, vinflunine plus best supportive care did not decrease health-related quality of life (P=.66).

“Given our current inability to significantly impact on most patient outcomes in the untreated metastatic setting, additional phase-3 trials in the salvage setting should be delayed until such time as clinically meaningful developments in our therapeutic armamentarium set the stage to demonstrate what we all hope will be a real chance of improving patient outcomes,” Dreicer wrote.

Bellmunt J. J Clin Oncol. 2009;doi:10.1200/JCO.2008.20.5534

Dreicer R. J Clin Oncol. 2009;doi:10.1200/JCO.2009.23.8071