IRVING, Texas, May 30, 2015 /PRNewswire/ -- Caris
Life Sciences® today announced the presentation of data from a
study in which researchers identified biomarker changes, including
key driver mutations, in 89% of metachronous paired glioma tumors,
indicating changes in response to therapy as the disease
progresses. The study observing 19 patients was a subset of a
larger study analyzing 1,245 glioma samples that confirmed
molecular heterogeneity of the cancer. These data utilizing Caris
Molecular Intelligence®, the company's panomic comprehensive tumor
profiling service, are being presented at the 2015 annual meeting
of the American Society of Clinical Oncology (ASCO) in Chicago, Ill.
"Paired data research is critically important to understanding
disease progression and predicting treatment resistance, which is a
type of analysis that has not been previously reported in
high-grade gliomas," said lead author of the study, Joanne Xiu, Ph.D., Research Scientist and
Molecular Science Liaison at Caris Life Sciences. "The
high-frequency of mutations observed over time explains why
high-grade gliomas can become resistant to new therapies,
demonstrating the need for a re-biopsy for tumor profiling to
direct the next line of therapy."
In this study (abstract #2058), paired tumors from 19 patients
(18 glioblastoma [GBM] and one grade III) were taken at an average
of 469 days apart. Researchers observed that 89% (17 pairs) had one
or more biomarker changes over time. The data showed that 23%
(3/13) lost MGMT-methylation (MGMT-ME), indicating acquired
resistance to temozolomide. Three tumor pairs also showed acquired
EGFR mutations or amplification. In the cohort observing 1,245
glioma samples, which included GBM and phase II-III tumors,
researchers observed epidermal growth factor receptor variant III
(EGFRvIII) exclusively in GBM, and MGMT ME in 47% of all tumors.
PD-L1 expression on tumor cells was seen in 27% and was more common
in tumors without MGMT ME (36% vs. 18%). PD-1 expression on
tumor-infiltrating lymphocytes was seen in 48% and was higher in
GBM than grade II-III.
"These results, from a large cohort of glioma samples, provide
us with insights into the biology of the disease, confirming the
heterogeneity of the cancer," said Santosh
Kesari, M.D., Ph.D., Director of Neuro-oncology at Moores
UCSD Cancer Center and author on the study. "Utilizing
comprehensive tumor profiling can inform physicians on how to make
better treatment decisions for patients based on the unique
characteristics of their tumor."
In a second paired tumor study (abstract #5545), researchers
used Caris Molecular Intelligence to retrospectively analyze
sequencing results from 83 epithelial ovarian carcinoma (EOC)
samples arising from different sites in an attempt to better
understand how to apply NGS in the management of the disease. The
samples were collected and observed from 43 to 2,793 days apart.
The study results showed that 85.5% of the mutations showed
complete agreement between the first and subsequent sample. Only 12
paired samples showed disagreement in gene results, and those
differences were only observed in one gene. The authors conclude
that use of molecular profiling in EOC offers a more comprehensive
approach to identifying additional therapeutic options and should
be studied further.
In a third paired tumor study (abstract #567), researchers
evaluated 337 cases with >1 asynchronous primary/metastatic
breast cancer (BC) molecular profiles and 40 cases with >1
synchronous molecular profiles. At the same institution,
researchers evaluated the samples for differences in ER, PR, and
HER2 status in the same or contralateral breast, and in primary vs.
locally recurrent or metastatic BCs. The author concludes that as a
result of the discordant results, tumor profiling should take place
at diagnosis and at each time of recurrence/progression in the
cancer continuum to more accurately reflect the tumor profile at
the time of treatment.
In a final paired tumor study (abstract #558), researchers
utilized comprehensive molecular profiling to analyze breast
cancers (BCs) at a single institution for differences in clonal
populations within the same breast, bilateral synchronous BCs,
and/or within primary and paired locally recurrent or metastatic
tumors. Gene alterations (GAs), identified by NGS, were compared in
9 synchronous BCs and 48 primary/recurrent paired BCs. Estrogen
receptor (ER), progesterone receptor (PR), androgen receptor (AR),
were evaluated by Immunohistochemistry (IHC) and HER2 was evaluated
by IHC and in situ hybridization (ISH). Researchers
identified that common GAs differ in both synchronous primary BCs
and in paired primary/metastatic tissues and such discordance could
influence treatment recommendations. These findings highlight the
molecular evolution of BC and the importance of evaluating
predictive markers of treatment benefit both in synchronous and
metastatic BCs.
About Caris Life Sciences®
Caris Life Sciences® is a
leading biotechnology company focused on fulfilling the promise of
precision medicine through quality and innovation. Caris Molecular
Intelligence®, the company's healthcare information and
comprehensive tumor profiling service with more than 70,000
patients profiled, provides oncologists with the most clinically
actionable treatment options available to personalize cancer care
today. Using a variety of advanced profiling technologies to assess
relevant biological changes in each patient's tumor, Caris
Molecular Intelligence connects biomarker data generated from a
tumor with biomarker-drug associations supported by evidence in the
relevant clinical literature. Since 2009, Caris has tracked
clinical and outcome data for certain patients undergoing tumor
molecular profiling, for which Caris has observed that patients
treated with drugs consistent with their molecular profile show a
significant increase in overall survival. The company is developing
its Carisome® TOP™ technology, a revolutionary and proprietary
blood-based platform for the development of novel therapeutics,
drug delivery and drug target identification. The technology is
also being developed for diagnosis, prognosis, and theranosis of
cancer and other complex diseases. Headquartered in Irving, Texas, Caris Life Sciences offers
services throughout Europe, the
U.S., Australia and other
international markets. To learn more, please visit
www.CarisLifeSciences.com.
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