Sysmex Inostics' SafeSEQ ER+/HER2- breast cancer panel demonstrates equivalent sensitivity to OncoBEAM(TM) enhanced digital PCR technology for detection of mutations in circulating tumor DNA

Hamburg/Baltimore (ots) - Recent data presented by Dr. Hope S.
Rugo from the University of California San Francisco on behalf of
investigators in the Translational Breast Cancer Research Consortium
at the American Association of Cancer Research 2019 meeting in
Atlanta, Georgia demonstrate how Sysmex Inostics' novel SafeSEQ
ER+/HER2- breast cancer panel can detect clinically relevant
mutations in circulating tumor DNA (ctDNA) from patients with
metastatic breast cancer with sensitivity equivalent to Sysmex's
highly clinically validated OncoBEAM liquid biopsy testing. Patients
in this study received two different dose levels of palbociclib, a
CDK4/6 inhibitor, in combination with either fulvestrant or
tamoxifen. In addition to tissue-based retinoblastoma protein
phosphorylation and Ki67 expression levels, mutations detected in
ctDNA were evaluated to determine correlation with response.
Overall, the results indicated that the presence of a PIK3CA mutation
in plasma was associated with worse outcome, while the presence of
ESR1 mutations in ctDNA did not appear to impact response to therapy.

Sixty-nine patients were evaluated by the SafeSEQ panel, of whom
52 (75%) had a mutation in ctDNA affecting PIK3CA, ESR1, TP53, ERBB2,
AKT1, or KRAS. Consistent with observed mutation rates for this
breast cancer subtype, 27 (39%) patients had a mutation in PIK3CA.
Additionally, 24 (35%) patients had mutation affecting ESR1, which
agrees with the expected mutation rate for this gene for patients who
have received aromatase inhibitor therapy. For patients with a
PIK3CA mutation, the median progression free survival (PFS) was 2.3
months, versus 9.7 months for patients who did not. However, there
was no significant difference in PFS for patients with an ESR1
mutation versus ESR1-wildtype patients, which is consistent with
previous studies that demonstrated the efficacy of palbociclib in
combination with hormone therapy regardless of ESR1 mutation status.

In addition to SafeSEQ testing, 35 patients had sufficient plasma
available for matched analysis using Sysmex Inostics OncoBEAM breast
cancer panel which is highly clinically validated for ultra-sensitive
detection of mutations affecting PIK3CA, AKT1, and ESR1 (limit of
detection 0.04% mutant allele frequency, MAF). A total of 54
positive calls across these three genes were successfully detected by
both assays (100% positive percent agreement), of which 22 (41%) were
below 1% MAF, and 5 (9%) were below 0.1% MAF for the OncoBEAM
reference method. Given numerous published studies which have
demonstrated decreased reliability of blood-based "pan-cancer"
next-generation sequencing tests below 1% MAF, the robust accuracy at
low allelic frequencies observed for SafeSEQ in this study
demonstrates the advantages of highly focused panels for defined
clinical intended uses. SafeSEQ's ability to deliver
ultra-sensitive blood-based detection of mutations in ctDNA is due to
its foundational technology which was specifically developed and
optimized for the detection of rare mutant molecules, an essential
capability for clinical ctDNA analysis.

Interestingly, for the 35 patients tested with both SafeSEQ and
OncoBEAM, the median MAF for AKT1 and PIK3CA mutations detected by
both tests was approximately 10%, while the median MAF for ESR1
mutations was below 1%. "The ability to evaluate mutations in blood
in patients with advanced hormone receptor positive breast cancer
profoundly impacts our ability to understand both response and
resistance and will allow delivery of more effective therapy",
commented Hope Rugo, the lead investigator for this trial. Dr. Rugo
noted that "a highly sensitive blood-based assay is even more
important now given recent positive data with a PI3K inhibitor in
patients with known mutations in this pathway, particularly given the
difficulty in obtaining tumor biopsies in this disease." Dr. Ben
Park, a senior investigator in the study commented, "Given the rising
interest in ESR1 mutation detection in plasma for various clinical
applications including possible therapeutic targets as well as
molecular monitoring of minimal residual disease for recurrence,
highly sensitive liquid biopsy tests capable of reliable detection at
ultra-low frequency are now more important than ever."

Presentation Details

Rugo, H.S. et al. (2019, April). Palbociclib in combination with
fulvestrant or tamoxifen as treatment for hormone receptor positive
metastatic breast cancer with prior chemotherapy for advanced disease
(TBCRC 035): A Phase II study with pharmacodynamic markers. Presented
at the American Association of Cancer Research annual conference,
Atlanta, Georgia.

This work was supported by Pfizer and the Translational Breast
Cancer Research Consortium.

About Sysmex Inostics

Sysmex Inostics, a subsidiary of Sysmex Corporation, is a
molecular diagnostic company that is a pioneer in blood-based
cell-free tumor DNA mutation detection in oncology utilizing highly
sensitive technologies such as OncoBEAM(TM) and SafeSEQ. These
technologies were initially developed by experts at the Johns Hopkins
School of Medicine over a decade ago and this deep expertise in ctDNA
analysis extends to the core of Sysmex Inostics' capabilities for
technology development and implementation.

With more than 10 years of experience in liquid biopsy Sysmex
Inostics is a trusted partner to leading pharmaceutical companies,
advancing their efforts to bring the most effective personalized
cancer therapies to global markets.

Sysmex Inostics' OncoBEAM(TM) and SafeSEQ services are readily
available to support clinical trials and research in oncology. In
addition, OncoBEAM(TM) tests are available through a CLIA certified
laboratory for routine clinical analysis as well as distributed as
kit products in EU.

Sysmex Inostics' headquarters and GCP Service Laboratory are
located in Hamburg Germany; Sysmex Inostics' CLIA-certified and GCP
Clinical Laboratory is located in Baltimore, Maryland. For more
information refer to www.sysmex-inostics.com or email
info@sysmex-inostics.com.

Contact:
Sysmex Inostics
Press Release
Phone: +49-(0)-40-3259070
Mail: info@sysmex-Inostics.com

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