ASH News Daily - Sunday, December 11, 2011 - (Page A-9)
Sunday, December 11, 2011
ASH NEWS DAILY
Page A–9
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BRAF and PARP – Acronyms to Remember From ASCO 2011
ASH/ASCO
By heatheR landau, Md
T
his year’s American Society
of Clinical Oncology meeting
will likely be remembered
as historical for the treatment of
melanoma. With the meeting falling
on the heels of the approval of
ipilimumab in March 2011, the audience
was ready for more melanoma
breakthroughs. So when Dr.
Paul B. Chapman, Memorial SloanKettering
Cancer Center, presented
the phase III results from a randomized
trial in newly diagnosed
patients with BRAF-mutated melanoma
showing increased response
rates and improved survival compared
to dacarbazine, the possibility
of another FDA-approved drug
for melanoma became a reality. Indeed,
the drug was FDA-approved
on August 17, 2011. After decades
of minimal and suboptimal therapy
for advanced disease, this progress
in melanoma is inspiring to all clinical
investigators. Today during the
ASH/ASCO Joint Symposium at
9:30 a.m. (Marriott Hall, San Diego
Marriott Marquis & Marina), Dr.
Chapman will share the results of
the BRIM3 study comparing the
BRAF inhibitor vemurafenib with
dacarbazine (DTIC) in patients with
V600EBRAF-mutated melanoma.
Now with two FDA drugs approved
for the treatment of melanoma
both showing survival benefits,
Dr. Chapman will likely be faced
with questions regarding the role
for vemurafenib versus ipilimumab
and is well poised to do so given his
involvement in the development of
both drugs. Looking ahead, issues
that will require consideration include
the need for upfront genotyping
of tumors (similar to lung cancer)
as well as careful assessment of
the toxicity profiles of these agents.
Dr. Jonathan A. Ledermann,
University College London Cancer
Institute and UCL Hospitals, will
follow Dr. Chapman with his presentation
on olaparib (AZD2281),
an oral PARP inhibitor that shows
promise as maintenance therapy in
patients with relapsed high-grade
serous ovarian cancer. The standard
practice in this setting is to observe
patients who respond to salvage
chemotherapy until further disease
progression, which inevitably
occurs. The phase II data demonstrating
markedly prolonged progression-free
survival (PFS) when
olaparib is compared with placebo
is therefore potentially practicechanging.
More time is certainly
needed to see how much this affects
survival, an important secondary
endpoint, especially for regulators.
The drug has been reformulated
into a tablet, which is easier for patients
to administer, and a new series
of studies will be launched with
the aim of regulatory approval. Dr.
Ledermann believes that the possibilities
for the drug are numerous,
such as second-line and first-line
maintenance as well as combination
studies with chemotherapy.
The next presentation will focus
on DNA based-strategies that are
emerging in order to identify targets
and tailor therapy in patients who
typically have low response rates
to salvage therapy. Dr. Apostolia
Maria Tsimberidou, MD Anderson
Cancer Center, will describe her
team’s initiative on personalized
medicine in a phase I clinical trials
program. She analyzed 1,144 patients
with advanced cancer treated
on phase I clinical trials and molecular
aberrations were identified in
40 percent of patients. Patients were
treated with matched therapy targeting
their molecular aberrations.
In patients with one aberration
identified, matched therapy (n=175)
compared with treatment without
matching (n=116) was associated
with a higher overall response rate,
longer time to treatment failure, and
longer survival. Although the study
was not randomized and patients
had diverse tumor types, identification
of specific molecular abnormalities
and selection of therapy based
on these abnormalities was associated
with improved outcomes compared
with the standard approach.
Dr. Tsimberidou and her team are
continuing to pursue this approach
»» ACRONYMS Page A-18
Congratulations
David G. Nathan, MD
on receiving the
Wallace H. Coulter Award for
Lifetime Achievement
in Hematology.
We celebrate your
remarkable career
which has combined
outstanding teaching,
pioneering research
and excellence in
clinical care.
to
DANA-FARBER/CHILDREN’S HOSPITAL CANCER CENTER
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