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T
here continues to be incredible excitement
in the melanoma field due to a constant
flow of advances and discoveries. I have
chosen three to share with you.
In the area of therapy, last year’s approval of
ipilimumab as adjuvant therapy for stage III
melanoma opened the door to a new era in
melanoma treatment. This approval was based
on the pivotal study by Eggermont et al (
Lancet
Oncol
2015;16:522-530). For a long time, there
has been an unmet need for an approved adjuvant
therapy for stage III melanoma patients besides
interferon, which is only marginally helpful and
very toxic. This multicentre and international
group performed a double-blind phase 3 trial with
951 patients with stage III cutaneous melanoma
who had not received previous therapy except
surgery. Patients were randomised to receive
intravenous ipilimumab (10 mg/kg) or saline
every 3 weeks for four doses and then every 3
months for 3 years. The group who received the
adjuvant ipilimumab had significantly improved
recurrence-free survival (median survival was
26.1 months, and 3-year survival was 46.5%)
versus the placebo group (median survival was
17.1 months, and 3-year survival was 34.8%).
Adverse events were immune-related and
resulted in discontinuation of therapy by 52%
of the patients receiving active therapy and 5
deaths.
Despite the toxicity of ipilimumab, the adjuvant
therapy clearly improved recurrence-free
survival. The dosage used of 10 mg/kg is higher
than the approved dose of 3 mg/kg that is
used in patients with stage IV disease. Further
investigation on dosing is ongoing in the ECOG
1609 (NCT 01274338) study that is comparing
1 year of ipilimumab at 10 mg/kg versus 3 mg/
kg versus high-dose interferon. So, stay tuned.
More information to come to help our stage III
melanoma patients!
Another major development in treating
melanoma is our new understanding of the
regulatory pathways and immune checkpoints
in the adaptive immune response to melanoma.
A wonderful review from the Moffitt Cancer
Center (United States) details how inhibitors
of these checkpoints can be utilised to treat
melanoma (
Semin Oncol
2015;42:363-377).
Blockades by an antibody to CTLA-4 or an
antibody to PD-1 have now been shown to
be successful strategies either alone or in
combination in melanoma patients. Other
emerging checkpoint proteins (BTLA, VISTA,
CD 160, LAG3, TIM3, CD244, and others) are
also being investigated as potential targets for
inhibition.
Finally, a recent paper by Kaisaki et al presents
data that may transform the way we diagnose
and follow our melanoma patients (
PLoS One
2016;11:e0162809). Imagine if we could draw
the blood of our melanoma patients to see how
they have responded to therapy. This study
suggests that might not be too far in the future.
This group studied circulating tumour DNA of
melanoma patients and lung cancer patients.
Solid tumours often release DNA into the
circulation and therefore the blood could be a
source for a “liquid” biopsy.
The 21 known melanoma patients were studied
retrospectively to confirmwhether themutations in
the primary melanoma would also be detectable in
the circulating tumour DNA. Blood samples were
drawn within 1 year of biopsy or before treatment.
Circulating DNA showed good concordance with
the primary melanoma mutations. Of note was
that circulating DNA sequenced after targeted
melanoma therapy demonstrated that in 9 out of
10 patients, the mutations were no longer found.
This suggests that circulating DNA could be a way
to follow therapeutic responses in our melanoma
patients!
A recent paper
by Kaisaki et al
presents data that
may transform the
way we diagnose and
follow our melanoma
patients. Imagine
if we could draw
the blood of our
melanoma patients
to see how they have
responded to therapy.
This study suggests
that might not be too
far in the future.
Dr Jane Grant-Kels
onmelanoma
Jane Grant-Kels MD is
Professor and founding
Chair of the Department of
Dermatology at the University
of Connecticut Health Center
and Medical School, and an
Advisory Board Member of
PracticeUpdate Dermatology.
She specialises in cutaneous
oncology and pigmented
lesions of the skin.
PRACTICEUPDATE RHEUMATOLOGY & DERMATOLOGY
2016 TOP STORIES IN DERMATOLOGY
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