basal cell carcinoma update - The Dermatologist

BASAL CELL CARCINOMA
UPDATE: RECENT RESEARCH
AND EMERGING TREATMENT
OPTIONS
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Two recent articles in the New England Journal of Medicine about vismodegib provide additional evidence for the use of the drug in the treatment of advanced BCC and new evidence for the
use of the drug in patients with basal cell nevus syndrome, and a new study from researchers in Boston further confirms that caffeine may help reduce an individual’s risk of developing BCC.
JULIA ERNST, MS, ASSISTANT EDITOR
developments for BCC. The efficacy of
vismodegib has been further supported
with the results of a recent study
in the New England Journal of Medicine
(NEJM), and another article in the
same issue of NEJM demonstrates that
the drug is also effective for patients
with the rare, heritable disease basal
cell nevus syndrome (BCNS), which
is sometimes referred to as Gorlin syndrome.
3,4 In addition, researchers have
demonstrated that caffeine consumption
may lower an individual’s risk for
developing BCC. 5,6,7
Basal cell carcinoma (BCC) is highly
curable when caught early and
treated quickly, but a delay in detecting
this common skin cancer or in
initiating treatment can lead to much
more severe disease. In January 2012,
vismodegib (Erivedge) was approved
for patients with severe disease and is a
novel treatment option that has, so far,
led to significant, positive results. 1,2
Recently, there have been a number
of noteworthy research and treatment
VISMODEGIB EFFICACY CONFIRMED IN NEW PHASE
II STUDY
Vismodegib is approved for adult
patients with metastatic or recurrent,
locally advanced BCC who were not
successfully treated with surgery or
who are not candidates for surgery or
radiation therapy. 1 In a Phase II study
of 104 patients with BCC (71 cases of
locally advanced BCC [laBCC] and
33 cases of metastatic BCC [mBCC]),
vismodegib shrank lesions in approximately
43% of patients with laBCC and
in about 30% of patients with mBCC. 2
Now, the results of a new Phase II trial
demonstrate that vismodegib increases
progression-free survival, promotes tumor
shrinkage and results in significant
response rates. 3
Working under the direction of lead
study author Axel Hauschild, MD, of
the Universitätsklinikum Schleswig-
Holstein in Kiel, Germany, a group of
researchers from around the world enrolled
104 patients, 33 with mBCC and
71 with laBCC, in a Phase II, two-cohort,
non-randomized study. 3 Patients
were treated with a once-daily, 150 mg
dose of vismodegib; dose interruption
was allowed for up to 4 weeks to allow
patients to recover from toxic effects. 3
The primary endpoint was the objective
response rate as assessed by independent
review. 3 Because a previ-
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ously defined standard endpoint for
laBCC did not exist when the study
was designed, the researchers defined
response “as a decrease of 30% or more
in the externally visible or radiographic
dimension (if applicable) or complete
resolution of ulceration (if present at
baseline).” 3 Progressive disease was defined
as “an increase of 20% or more
in the externally visible or radiographic
dimensions (if applicable), new ulceration
or a new lesion.” 3
Patients with mBCC all had partial
responses; according to the researchers,
the majority of these patients (24/33, or
73%) had tumor shrinkage. 3 The median
duration of objective response in these
mBCC patients was 7.6 months (range,
2.1 to 11.1), according to independent
review, and investigator-determined response
duration was 12.9 months (range,
1.9 to 12.9). 3 Median progression-free
survival was 9.5 months (95% confidence
interval [CI], 7.4 to not estimable),
according to independent review,
and 9.2 months (95% CI, 7.4 to not estimable),
according to the estimates of the
site investigators. 3 Overall survival data
were not mature at the time the study
was published. 3
Patients with laBCC had an objective
response rate of 43%. 3 A complete
response, defined as the absence of residual
BCC on assessment of a biopsy
specimen, was observed in 13 patients
(21%). 3 The median duration of response
was 7.6 months (range, 1.0 to
12.9 months), according to independent
review, and 7.6 months (range, 1.4
to 16.6 months), according to the site
investigators. 3 Biopsy specimens from
54% of patients in this cohort showed
no residual BCC, and visible reductions
in tumor size and improvement in appearance
were noted by site investigators
for the majority of these patients. 3
According to the researchers, all patients
experienced at least one adverse
event (AE) during the study; more than
half of the treated patients (57%) had
only Grade 1 or 2 events. 3 Grade 3 and
4 AEs included muscle spasms, weight
loss, fatigue and loss of appetite. 3 Of
the 104 total patients, 13 (12%) experienced
an AE that led to discontinuation
of vismodegib. 3
Serious AEs were reported in 26
patients (25%). 3 Fatal adverse events
(Grade 5) were reported in seven patients
(one with mBCC and six with
laBCC): death from an unknown cause
(in three patients) and hypovolemic
shock, myocardial infarction, meningeal
disease and ischemic stroke (in one
patient each). 3
According to Ervin Epstein, MD, of
Children’s Hospital Oakland Research
Institute (CHORI) in Oakland, CA,
the results of this worldwide study show
“significant clinical benefit for the use
of the drug in patients with locally advanced
and metastatic disease.” Dr. Epstein’s
research focuses on non-melanoma
skin cancer, particularly BCC.
VISMODEGIB DEMONSTRATES POSITIVE INITIAL
RESULTS FOR PATIENTS WITH BASAL CELL NEVUS
SYNDROME
BCNS is a rare, heritable condition
that can lead to the development of
hundreds to thousands of BCCs in a
single patient. 4 Individuals with BCNS
are also at an increased risk for meduloblastomas
and rhabdomyosarcomas. 4
Currently, there is no pharmacologic
therapy for patients with BCNS, but
the second article published in NEJM
reports that vismodegib may also be effective
for patients with the syndrome. 4
The Phase II trial enrolled 42 patients
with BCNS, all of whom had at
least 10 surgically eligible BCCs present
at study entry or removed during
the previous 2 years. 4 Participants were
randomized to receive either oral vismodegib
at a dose of 150 mg daily or
placebo for 18 months. 4
The researchers tracked more than
2,000 existing and 694 new, surgically
eligible BCCs. 4 Vismodegib was found
to significantly reduce “the per-patient
rate of new surgically eligible basal
cell carcinomas below that of the placebo
group (mean, 2 vs. 29 new surgically
eligible basal cell carcinomas per
year; median, 2 vs. 25 new surgically
eligible basal cell carcinomas per year;
P

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Erin Gilbert, MD, PhD, an assistant
professor of dermatology at
SUNY Downstate Medical Center in
New York, NY, who is in practice at
Gramercy Park Dermatology in New
York, concurs.
“Ongoing treatment with vismodegib
holds promise for those patients
with basal cell nevus syndrome who
can tolerate the medication,” Dr. Gilbert
explains. “Our primary concern
is about longer term exposures to the
drug and about the burden of cancer
when and if their treatment is stopped.”
While the drug did lead to side effects,
according to Dr. Epstein, including
leg cramps and hair and weight
loss, the AEs reported in patients with
BCNS were similar to those experienced
by patients receiving vismodegib
in other trials. 4
Dr. Epstein is conducting ongoing
studies in patients with multiple BCCs,
especially individuals with BCNS.
Readers interested in the trial can contact
Maria Acosta, administrative coordinator
at CHORI, for more information
at macosta@chori.org.
Photo courtesy of Robert H. Johr, MD
and Women’s. 5 Women’s and Harvard Medical School.
Nearly 113,000 participants
STUDY PROVIDES NEW EVIDENCE FOR LINK BE-
TWEEN CAFFEINE CONSUMPTION AND DECREASED
RISK OF NON-MELANOMA SKIN CANCER
An accumulating body of research
demonstrates the health benefits of caffeine.
In October 2011, a team from
Brigham and Women’s Hospital and
Harvard University showed that increased
consumption of coffee led to
a decrease in risk for non-melanoma
skin cancer (NMSC). 5 A new study
from another team at Brigham and
Women’s further confirms the link between
caffeine and a decreased risk of
NMSC, particularly BCC. 6,7
Lead researcher Jiali Han, PhD, an
(112,897) were included in the present
analysis; 22,786 developed BCC over
the 20-plus years of study follow-up. 6
The researchers observed an inverse association
between all coffee consumption
and the risk of BCC. 6 According
to an abstract on the study in Cancer
Research, “compared with individuals
who consumed caffeinated coffee less
than 1 cup per month, women who
consumed more than 3 cups/d had
the lowest risk (RR, 0.79; 95% CI,
0.74–0.85; P trend
< 0.0001) and the RR
for men was 0.90 (95% CI, 0.80–1.01;
P trend
=0.003).” The abstract notes that
caffeine from other sources, including
tea, cola and chocolate, was also
associate professor at Brigham and
Women’s, Harvard Medical School and
Harvard School of Public Health, and
colleagues conducted a prospective
analysis of data from the Nurses’ Health
inversely associated with BCC risk. 7
Decaffeinated coffee did not lead to a
decreased risk of BCC. 7
“Given the nearly 1 million new
Study and the Health Professionals cases of BCC diagnosed each year in
Follow-Up Study, both of which are
large, long-running studies investigating
the factors that influence women’s
and men’s health, respectively. 6 The
Nurses’ Health Study was also used for
the October 2011 study from Brigham
the United States, daily dietary factors
with even small protective effects
may have great public health impact,”
explains researcher Fengju Song, PhD,
a postdoctoral fellow in the department
of dermatology at Brigham and
“Our study indicates that coffee consumption
may be an important option
to help prevent BCC.” n
References
1. National Cancer Institute. FDA approval for
vismodegib. Available at: http://www.cancer.gov/
cancertopics/druginfo/fda-vismodegib. Accessibility
verified July 10, 2012.
2. The Dermatologist. News and Trends: FDA approves
Erivedge for advanced basal cell carcinoma. Available
at: http://the-dermatologist.com/content/newsand-trends-2.
Accessibility verified July 10, 2012.
3. Sekulic A, Migden MR, Oro AE, et al. Efficacy
and safety of vismodegib in advanced basal cell carcinoma.
N Engl J Med. 2012;366(23):2171-2179.
4. Tang JY, Mackay-Wiggan JM, Aszterbaum M,
et al. Inhibiting the hedgehog pathway in patients
with the basal cell nevus syndrome. N Engl J Med.
2012;366(23):2180-2188.
5. The Dermatologist. Additional evidence for the
link between caffeine and decreased skin cancer
risk. Available at: http://the-dermatologist.com/
content/additional-evidence-link-between-caffeine-and-decreased-skin-cancer-risk.
Accessibility
verified July 10, 2012.
6. American Association for Cancer Research. Coffee
consumption inversely associated with risk of most
common form of skin cancer. Available at: http://www.
aacr.org/home/public--media/aacr-press-releases.
aspx?d=2513. Accessibility verified July 10, 2012.
7. Song F, Qureshi AA, Han J. Increased caffeine
intake is associated with reduced risk of
basal cell carcinoma of the skin. Cancer Res.
2012;72(13):3282-3289.
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