Vinflunine Fails to Improve OS in Metastatic Breast Cancer

Vinflunine did not improve overall survival compared with physician’s choice of alkylating agent in patients with heavily pretreated metastatic breast cancer, according to results of an open-label phase III trial.

“Chemotherapy is the backbone of therapy for patients with metastatic breast cancer previously treated with or ineligible for endocrine therapy,” wrote study authors led by Javier Cortes, MD, PhD, of Ramon y Cajal University Hospital in Madrid. “Ultimately, however, the majority of patients either do not respond or develop resistance to these treatments. For heavily pretreated patients, there remains a critical need for new agents with a better benefit/risk ratio.”

The trial compared the microtubule inhibitor vinflunine 280 mg/m² on day 1 of each 3-week cycle vs physician’s choice of alkylating agent, including cyclophosphamide, melphalan, mitomycin C, thiotepa, cisplatin, or carboplatin. A total of 594 patients were included (298 vinflunine, 296 alkylating agent). The results were published in Annals of Oncology.

The hazard ratio (HR) for overall survival (OS) was 1.04 (95% CI, 0.86–1.25; P = .67). The median OS was 9.1 months with vinflunine and 9.3 months with the alkylating agent. Similarly, the HR for progression-free survival (PFS) was 0.94 (95% CI, 0.80–1.12; P = .49). Median PFS was 2.5 months with vinflunine and 1.9 months with the alkylating agent.

The objective response rate was also similar, at 6% with vinflunine and 4% with the alkylating agent. However, the disease control rate was better with vinflunine, at 44% compared with 35% (P = .04). Time to first response was also numerically shorter with vinflunine.

A quality-of-life analysis showed that global health status decreased at all points after baseline in both treatment groups, with a more pronounced decrease with the alkylating agent than with vinflunine.

Grade 3/4 adverse events (AEs) were reported in 48% of vinflunine patients, and in 38% of alkylating agent patients. The most common such AEs with the study drug were asthenia and neutropenia, while with alkylating agents they were most commonly neutropenia and thrombocytopenia. There were 6 fatal AEs within 30 days of the last administration, but none were considered related to the treatment. Serious AEs occurred in 28% of vinflunine patients and in 23% of alkylating agent patients, and 7% and 8%, respectively, discontinued treatment due to an AE.

“The low response rates, short PFS, and OS of 9 months emphasize the dismal prognosis for these patients and the need for better treatment options,” the authors wrote. “Nevertheless, the favorable tolerability profile of vinflunine in heavily pretreated metastatic breast cancer may support evaluation in an earlier treatment setting using a higher dose of vinflunine.”