Press Release: Novartis investigational BYL719 (alpelisib) plus fulvestrant consistently improved PFS in patients with PIK3CA mutated HR+/HER2- advanced brea...
Novartis International AG / Novartis investigational BYL719 (alpelisib)
plus fulvestrant consistently improved PFS in patients with PIK3CA
mutated HR+/HER2- advanced breast cancer in new SOLAR-1 analyses.
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responsible for the content of this announcement.
-- BYL719 plus fulvestrant meaningfully prolonged PFS vs fulvestrant alone
in patients with PIK3CA mutated HR+/HER2- advanced breast cancer after
progression on an aromatase inhibitor or after receiving up to one
additional line of therapy
-- SOLAR-1 is the first Phase III breast cancer trial to demonstrate
potential viability of using liquid biopsy to select patients for
-- Novartis continues to invest in flexible genomic profiling solutions to
identify the approximately 40% of HR+ advanced breast cancer patients
with a PIK3CA mutation who may benefit from targeted therapy
Basel, December 6, 2018 - Novartis today announced additional analysis
from the global Phase III SOLAR-1 trial investigating the alpha-specific
PI3K inhibitor BYL719 (alpelisib) in combination with fulvestrant in men
and postmenopausal women with PIK3CA mutated hormone receptor positive,
human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced
or metastatic breast cancer.
In SOLAR-1, the addition of BYL719 to fulvestrant nearly doubled median
progression-free survival (PFS) in patients with PIK3CA mutated
HR+/HER2- advanced breast cancer who progressed on or after an aromatase
inhibitor (AI) compared to fulvestrant alone. In this analysis, BYL719
plus fulvestrant also showed consistent clinically meaningful treatment
benefit after progression on an AI or after receiving up to one
additional line of therapy for advanced breast cancer. These data
will be presented today during an oral presentation at the 2018 San
Antonio Breast Cancer Symposium (SABCS) (Abstract #GS3-08).
Approximately 40% of patients living with HR+ advanced breast cancer
have a PIK3CA mutation, which over activates the PI3K pathway. When
activated, the PI3K pathway is associated with tumor growth, resistance
to endocrine treatment and a poor overall prognosis,. Currently
there are no approved treatments for breast cancer that specifically
target this mutation.
"PIK3CA mutation is the most common actionable alteration in ER+ breast
cancer, so it is encouraging to see a meaningfully prolonged PFS with
BYL719 combination therapy in patients with PIK3CA mutated breast cancer
who progressed on an aromatase inhibitor and who received up to one
additional line of therapy prior to treatment with BYL719 plus
fulvestrant," said Dejan Juric, MD, Director, Termeer Center for
Targeted Therapies, Massachusetts General Hospital Cancer Center. "With
the SOLAR-1 trial results, we can confidently say that identifying and
targeting PIK3CA mutations is clinically important as we apply the
precision oncology paradigm to breast cancer and continuously look for
new treatment solutions to extend the lives of patients with this
BYL719 in combination with fulvestrant consistently improved median PFS
in patients with PIK3CA mutated HR+/HER2- advanced breast cancer who
progressed within 12 months of AI treatment (mPFS: 11.0 months vs 6.8
months for fulvestrant alone) or received up to one additional line of
therapy for advanced breast cancer (mPFS: 10.9 months vs 3.7 months,
Most adverse events were mild to moderate in severity and generally
manageable through dose interruption, dose reductions and medical
management. Treatment discontinuation rate due to adverse events in
those with a PIK3CA mutation receiving BYL719 plus fulvestrant was 3%
compared to 2% for fulvestrant alone. The most frequent all-grade
adverse events (>=40%) were hyperglycemia (65% vs 9%), diarrhea (54% vs
11%), nausea (46% vs 20%) and rash (40% vs 6%). The most common grade
3/4 events (>=10%) were hyperglycemia (37% vs <1%) and rash (13% vs
Mutation status of participants in SOLAR-1 was identified by a clinical
trial assay developed by Qiagen(*). A significant PFS benefit was
observed for BYL719 plus fulvestrant in patients with a PIK3CA mutation
regardless of whether the mutation was identified by a tumor tissue test
or ctDNA test, suggesting the potential viability of using liquid
biopsies to identify PIK3CA mutation status (tissue positive HR=0.65;
mPFS 11.0 months; plasma positive HR=0.56; mPFS 10.9 months).
Novartis has entered into agreements with both Qiagen and Foundation
Medicine(**) to develop flexible companion diagnostic solutions for
BYL719 that utilize both tumor tissue and plasma sample types.
"Our work to develop an effective PI3K inhibitor started more than two
decades ago, and learning from multiple clinical trial experiences, we
have been able to advance an investigational targeted therapy for
patients with this specific breast cancer," said Samit Hirawat, MD, Head,
Novartis Oncology Global Drug Development. "SOLAR-1 is the first breast
cancer trial to show potential utility of liquid biopsies. We are
excited to collaborate with Qiagen and Foundation Medicine on tissue and
plasma tests that, if approved, may help oncologists identify patients
who could benefit from BYL719 plus fulvestrant."
The SOLAR-1 trial is ongoing to evaluate secondary endpoints, including
overall survival and will be presented and discussed in the future.
Overall survival (OS) results were immature at the time of data cut-off
after 52% of events (HR=0.73; 95% CI 0.48-1.10; p=0.06; median not
estimable vs 26.9 months). The prespecified O'Brien-Fleming stopping
boundary was not crossed. Discussions with health authorities regarding
the SOLAR-1 data have begun.
SOLAR-1 is a global, Phase III randomized, double-blind,
placebo-controlled trial studying investigational BYL719 in combination
with fulvestrant for postmenopausal women with PIK3CA-mutated HR+/HER2-
advanced or metastatic breast cancer that progressed on or following
aromatase inhibitor treatment with or without a CDK4/6 inhibitor.
The trial randomized 572 patients. Patients were allocated based on
tumor tissue assessment to either a PIK3CA-mutated cohort or a PIK3CA
non-mutated cohort. Within each cohort, patients were randomized in a
1:1 ratio to receive continuous oral treatment with BYL719 (300mg once
daily) plus fulvestrant (500 mg every 28 days + Cycle 1 Day 15) or
placebo plus fulvestrant. Stratification was based on visceral
metastases and prior CDK4/6 inhibitor treatment.
The primary endpoint is local investigator assessed PFS using RECIST 1.1
for patients with a PIK3CA mutation. Secondary endpoints include but are
not limited to overall survival, overall response rate, clinical benefit
rate, health-related quality of life, efficacy in PIK3CA non-mutated
cohort, safety and tolerability.
For the primary SOLAR-1 analysis, mutation status was determined by
tumor tissue via polymerase chain reaction (PCR) analysis. Plasma ctDNA
samples were also collected at baseline as a secondary endpoint. Plasma
ctDNA mutation status of participants in SOLAR-1 was identified by an
assay developed by Qiagen.
About BYL719 (alpelisib)
BYL719 is an investigational, orally bioavailable, alpha-specific PI3K
inhibitor. In breast cancer cell lines harboring PIK3CA mutations,
BYL719 has been shown to potentially inhibit the PI3K pathway and have
antiproliferative effects. In addition, cancer cell lines with PIK3CA
mutations were more sensitive to BYL719 than those without the mutation
across a broad range of different cancers.
About Novartis in Advanced Breast Cancer
For more than 30 years, Novartis has been tackling breast cancer with
superior science, great collaboration and a passion for transforming
patient care. With one of the most diverse breast cancer pipelines and
one of the largest numbers of breast cancer compounds in development,
Novartis leads the industry in discovery of new therapies and
combinations, especially in HR+ advanced breast cancer, the most common
form of the disease.
This press release contains forward-looking statements within the
meaning of the United States Private Securities Litigation Reform Act of
1995. Forward-looking statements can generally be identified by words
such as "potential," "can," "will," "plan," "expect," "anticipate,"
"look forward," "believe," "committed," "investigational," "pipeline,"
"launch," "encouraging," or similar terms, or by express or implied
discussions regarding potential marketing approvals, new indications or
labeling for BYL719 or the other investigational or approved products
described in this press release, or regarding potential future revenues
from such products. You should not place undue reliance on these
statements. Such forward-looking statements are based on our current
beliefs and expectations regarding future events, and are subject to
significant known and unknown risks and uncertainties. Should one or
more of these risks or uncertainties materialize, or should underlying
assumptions prove incorrect, actual results may vary materially from
those set forth in the forward-looking statements. There can be no
guarantee that BYL719 or the other investigational or approved products
described in this press release will be submitted or approved for sale
or for any additional indications or labeling in any market, or at any
particular time. Nor can there be any guarantee that BYL719 or such
other products will be commercially successful in the future. In
particular, our expectations regarding BYL719 and such other products
could be affected by, among other things, the uncertainties inherent in
research and development, including clinical trial results and
additional analysis of existing clinical data; regulatory actions or
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