FDA Approves First Combo Therapy for Advanced Melanoma
The FDA has approved trametinib (Mekinist, GlaxoSmithKline)
in combination with dabrafenib (Tafinlar, GlaxoSmithKline) to
treat patients with advanced melanoma that is unresectable or
metastatic. The safety and effectiveness of Mekinist in combination
with Tafinlar were demonstrated in a clinical trial of 162
participants with unresectable or metastatic melanoma with the
BRAF V600E or V600K mutation, most of who had not received
prior therapy. Results showed that 76% of participants treated
with Mekinist in combination with Tafinlar had their cancers
shrink or disappear, an objective response lasting an average
of 10.5 months. Fever, chills, fatigue, rash, nausea, vomiting,
diarrhea, abdominal pain, peripheral edema, cough, headache,
joint pain, night sweats, decreased appetite, constipation, and
muscle pain were the most common side effects reported by
participants receiving Mekinist in combination with Tafinlar.
Long-Term Efficacy and Safety of Alemtuzumab in Advanced Primary Cutaneous T-Cell Lymphomas
The British Journal of Dermatology (Vol. 170 Issue 2) has published
a study designed to assess the efficacy and safety of
alemtuzumab in the treatment of advanced CTCL. The study
was a multicenter retrospective analysis of 39 patients with
advanced CTCL treated with alemtuzumab between 2003 and
2013. Twenty-three of the patients had Sézary syndrome while
sixteen had advanced mycosis fungoides. All patients received
alemtuzumab 30 mg 2 to 3 times a week for a median duration
of 12 weeks. Fifteen patients received maintenance therapy
for a median duration of 24 weeks. Eleven patients (28%) had
transformed disease. After a median follow-up of 24 months,
8 patients (21%) were still alive. The overall response rate was
51% in the whole study group, 70% in patients with Sézary
syndrome and 25% in patients with mycosis fungoides. The
median time to progression was 3.4 months. Six patients remained
progression-free for more than 2 years. Five patients
experienced cutaneous large T-cell transformation during
alemtuzumab treatment and 1 patient developed primary cutaneous
large B-cell lymphoma. Twenty-four patients (62%) had
a grade 3 or higher infectious adverse event and 10 (26%) a
hematologic toxicity that led to treatment discontinuation in 17
cases (44%) and death in 2 (5%).
The study authors concluded that Alemtuzumab may induce
long-term remissions in Sézary syndrome but does not seem
effective in mycosis fungoides and transformed CTCL.
Cutaneous Delayed-Type Hypersensitivity in Patients With Atopic Dermatitis to Surfactants
A recent study by Cristin N. Shaughnessy, BS, Dana Malajian, BA,
Donald V. Belsito, MD sought to assess whether atopic patients
were more likely than nonatopic patients to patch test positive
to the surfactants cocamidopropyl betaine (CAPB) and cocamide
diethanolamide (DEA), or to the surfactant precursor amidoamine.
Patients with atopic dermatitis (AD) have abnormalities
in skin barrier function, and are predisposed to developing cutaneous
delayed-type hypersensitivity. Soap and detergents are
known to exacerbate the breakdown of the skin barrier.
The study looked at 1674 patients who underwent patch testing
to the North American Contact Dermatitis Group standard
screening series. The incidence of positive patch test results to
CAPB, cocamide DEA, and amidoamine among patients with
AD (n = 242) and without AD (n = 1422) was assessed. The data
show that AD was associated with contact hypersensitivity to
CAPB, but not to cocamide DEA or amidoamine. The study
authors concluded that patients with AD should avoid the use
of skincare products containing the surfactant CAPB.
Tazarotene in Patients With Basal Cell Nevus Syndrome
A recent report by Y. Tang, Albert S. Chiou, Julian M. Mackay-
Wiggan, Michelle Aszterbaum, Anita M Chanana, Wayne Lee,
Joselyn Lindgren, Maria Acosta Raphael, Bobbye J. Thompson,
David R. Bickers, and Ervin Epstein discusses the results
of a randomized, double-blind, vehicle-controlled study in
basal cell nevus (Gorlin) syndrome patients evaluating the efficacy
of topically applied tazarotene for basal cell carcinoma
chemoprevention (N=34 subjects), along with an open-label
trial evaluating tazarotene’s efficacy for chemotherapy of BCC
lesions (N=36 subjects) for a maximum follow-up period of
3 years. The authors of the study found that only 6% of patients
had a chemopreventive response and that only 6% of
treated BCC target lesions were clinically cured. The study also
provided no evidence for either chemopreventive or chemotherapeutic
effect of tazarotene against BCCs in patients with
BCNS. The authors hypothesize that the discrepancy between
the efficacy seen in Ptch1+/- mice as compared to that seen in
PTCH1+/-, BCNS patients, may relate to the superior barrier
function of human skin and the greater depth of human BCCs.
