P&T Highlights PV-10 in Coverage of Second European Post-Chicago Melanoma Meeting 2012
Monday September 17, 2012
The Meeting Highlights section of the September 2012 edition of Pharmacy and Therapeutics, (Vol. 37, No. 9, pgs. 527-528), covers selected sessions from the 2nd European Post-Chicago Melanoma Meeting 2012, including the session on intralesional PV-10.
The article is available from the P&T website at
www.ptcommunity.com/ptjournal/fulltext/37/9/PTJ3709526.pdf.
The PV-10 section of the article (may be easier to read at the link):
Intralesional Rose Bengal (PV-10)
• Sanjiv S. Agarwala, MD, Professor of Medicine, Temple
University School of Medicine, Philadelphia, Pa.; and Chief,
Oncology & Hematology, St. Luke’s Cancer Center,
Bethlehem, Pa.
• Vernon K. Sondak, MD, Chair, Department of Cutaneous
Oncology, H. Lee Moffit Cancer Center, Tampa, Fla.
PV-10 is a sterile, non-pyrogenic solution of Rose Bengal
disodium
(10% RB) for intralesional injection. It has an
established safety history in prior diagnostic and ophthalmic
use. PV-10 is not metabolized; it has a short circulatory halflife
of about 20 minutes. PV-10 is excreted via bile. It accumulates
selectively in the lysosomes of cancer cells and elicits autolysis
within 30 to 60 minutes.
Dr. Agarwala’s seven-center phase 2 trial in the U.S. and
Australia enrolled 80 patients with stage III/IV melanoma. The
median age of the patients was 70.0 years, and 61% were men.
In this study, which was completed in June 2012, investigators
treated up to 10 target lesions and observed one or two
untreated bystander lesions. Re-treatment of new or partially
responsive lesions was allowed as necessary.
Subjects received from one to four treatments (median, two
treatments). The median dose was 1.6 mL, and the median
cumulative dose was 3.4 mL. Adverse events were predominantly
locoregional and mild to moderate. No grade 4 or 5
events were reported, but there were seven reports of grade
3 injection-site pain.
The objective response rate (defined as complete response
+ partial response) was 58% in target lesions and 40% in bystander
lesions. Locoregional disease control (defined as the
addition of stable disease to complete and partial responses)
was reported for 80% of the target lesions and for 60% of the
bystander lesions. Bystander effects in untreated lesions correlated
closely with responses in injected lesions. A systemic
response was defined as stasis or regression of distant visceral
lesions in several patients.
The new analysis reported by Dr. Agarwala focused on responses
of target lesions stratified according to disease stage.
Stage III melanoma subjects exhibited consistently robust
responses to PV-10. Furthermore, responses were significantly
more durable in stage III patients (mean, 9.6+ months)
compared with 3.1 months for stage IV melanoma patients
(P < 0.001).
Response rates in stage IV patients were adversely affected
by greater target tumor burden at baseline and by the
progression of non-study lesions that precluded repeated
treatment.
Dr. Agarwala noted that the planned phase 3 trial of PV-10
will include about 180 subjects with stage IIIb and IIIc disease.
In an interview, Dr. Sondak noted that locally or regionally
advanced tumors without metastatic disease can be a severe
problem for patients and for surgeons.
“The logical approach is a localized one,” he said.
However, whereas radiation would be the obvious solution
for many cancers, melanoma is notoriously poorly responsive
to this treatment. Fortunately, Dr. Sondak said, a number of
tools have come along to treat this group of patients; some—
like V-TEK (OncovexGM-CSF) and PV-10—create an immune
effect.
He said further, “If it’s shown that they are causing local
destruction of tumors and are causing T-cell infiltrates, I’m
interested in seeing how I can take advantage of that. If phase
3 trials confirm their benefits, adding systemic immunological
therapies like ipilimumab and PD-1 with intralesional injection
therapies would be an extremely logical combination.” |
