VinCaP: a phase II trial of vinflunine in locally advanced and metastatic squamous carcinoma of the penis

Abstract

Background: We investigated the first-line activity of vinflunine in patients with penis cancer. Cisplatin-based combinations are commonly used, but survival is not prolonged; many patients are unfit for such treatment or experience toxicity that outweighs clinical benefit.

Methods: Twenty-five patients with inoperable squamous carcinoma of the penis were recruited to a single-arm, Fleming-A'Hern exact phase II trial. Treatment comprised 4 cycles of vinflunine 320 mg/m², given every 21 days. Primary endpoint was clinical benefit rate (CBR: objective responses plus stable disease) assessed after 4 cycles. Seven or more objective responses or disease stabilisations observed in 22 evaluable participants would exclude a CBR of <15%, with a true CBR of >40% being probable.

Results: Twenty-two participants were evaluable. Ten objective responses or disease stabilisations were confirmed. CBR was 45.5%, meeting the primary endpoint; partial response rate was 27.3%. Seven patients received >4 cycles of vinflunine. Dose reduction or treatment delay was required for 20% of cycles. In all, 68% of patients experienced at least one grade 3 adverse event. Two deaths on treatment were not caused by disease progression.

Conclusions: Pre-specified clinical activity threshold was exceeded. Toxicity was in keeping with experience in other tumours. Vinflunine merits further study in this disease.

Trial registration: NCT02057913.

Fig. 1

Consort diagram showing patient flow through the trial and the number of patients included in the analysis populations.

Fig. 2

Treatment duration showing timing of treatment, progression and death for all patients by responder status.

Fig. 3. Kaplan–Meier survival curves.

a progression-free survival (PFS) b overall survival (OS). Both curves are shown with associated 95% confidence bands estimated in the intention-to-treat population. N at risk (events) shows the number of patients who remain in each analysis set at a given time point and the number of PFS/OS events reported between times.