Platinum-based combination chemotherapy regimens have been the standard for metastatic penile cancer and do have some clinical activity. However, as the authors note, toxicity limits their value for patients with metastatic disease. In this study (VinCaP), they aimed to define both the toxicity and the disease control rate for the non-platinum cytotoxic agent Vinflunine as an alternative to platinum-based therapy. Vinflunine is a 3rd generation vinca alkaloid used as a second-line agent for metastatic urothelial cancer that has failed platinum-based chemotherapy.
Study Design: Phase II single-arm study in 8 UK centres (June 2014-May 2017)
Study Population: Men with measurable, histologically-proven squamous cell carcinoma (SCC) of the penis
• All men staged M1
• Men stage M0,Tx,N3
• Men stage M0,Tx,N2 and deemed inoperable by multidisciplinary team
• Men stage M0, T4 any N, ECOG performance status 0-2 and adequate hepatic and renal function
Hence, this was for patients with metastatic disease or locally advanced inoperable disease
Protocol: Men were treated with 4 21-day cycles of vinflunine (320mg/m2).
In 22 evaluable patients ≥7 responses/stabilisations were required to conclude a clinical benefit rate (CBR) [including complete response, partial response or stable disease (CR/PR/SD)] of at least 40% and exclude a rate of < 15% (p0 = 0.15, p1 = 0.40, α = 0.05, β = 0.80, Fleming-A’Hern exact design)
Primary endpoint was clinical benefit rate (CBR) after 4 cycles of vinflunine
Secondary endpoints included objective response rate (ORR = CR + PR), safety, tolerability, progression-free survival (PFS) and overall survival (OS)
They recruited 25 patients (median age 68 years) from 8 UK centers. Of these, 19 patients were M1; the remaining 6 had nodal disease. 17 patients had no residual disease in the penis itself. Median time from primary diagnosis was 4.9 months. Most were ECOG 0-1 (88%).
Only 22 of 25 patients received treatment. Recruitment halted in Sep 2016 to investigate 2 treatment-related deaths (1 sepsis, not neutropenic; 1 neutropenic, not septic); after review, the trial was re-opened Nov 2016.
In terms of tolerability and safety, 15 (68%) experienced grade 3/4 adverse events (AE); neutropenia was the most common AE (n = 5, 23%). Treatment compliance was moderate – 13 patients either never started or discontinued early; only 12 received 4+ cycles. 3 patients never started treatment, so were not part of the “evaluable population.” Of the remaining 22 patients, only 17 had measurable disease (3 patients discontinued, 2 died), and were called the “measurable population.”
In terms of clinical benefit, CBR = 45.5%, 95%CI: 24.4-67.8, in the evaluable population (n = 22). ORR on the other hand was 27.3%, (10.7-50.2) in evaluable population and 35.5%, (14.2-61.7) in measurable population (n = 17).
Median PFS: 2.9 months, 95%CI: 1.4-6.4; 12 month PFS: 16.7% (4.6-35.3). Median OS: 8.4 months, (3.2-14.1); 12 month OS: 33.7%, (15.4-53.1).
While the CBR exceeded the threshold to recommend further research and ORR was comparable to other recent phase II trials in penis cancer, the toxicity profile is significant – but consistent with known profile for vinflunine.
They consider this a positive trial and recommend vinflunine as an active agent in the treatment of locally advanced and metastatic SCC of the penis. However, phase III trials are still warranted to compare it to current standard of care.
Presented by: Lisa M. Pickering, MD
Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, Twitter: @tchandra_uromd at the 2018 ASCO Annual Meeting - June 1-5, 2018 – Chicago, IL USA