SINGAPORE - Media OutReach - 1 March 2021 - Novartis announced
the Health Sciences Authority (HSA) has approved* Piqray®, an
α-specific class I phosphatidylinositol-3-kinase (PIK3CA) inhibitor, for
the treatment of postmenopausal women, and men, with hormone receptor
positive (HR+), human epidermal growth factor receptor 2 (HER2-)
negative, advanced breast cancer with a PIK3CA mutation in combination
with fulvestrant after disease progression following an endocrine-based
regimen.1
"Novartis has been researching the
role of the PIK3CA mutation for more than 20 years and studying how to
target this mutation in order to delay disease progression," said
Itsaraet Gosriwatana, Oncology General Manager, Novartis (Singapore).
"The understanding of the PIK3CA status is crucial in equipping doctors
to develop a better personalized treatment plan for patients. Today, we
are pleased to be able to offer patients in Singapore with PIQRAY, an
important new therapy for HR+/HER2- advanced breast cancer patients
whose tumours have a PIK3CA mutation."
HSA approval is
based on results of the Phase III trial, SOLAR-1, that showed Piqray
plus fulvestrant nearly doubled median progression-free survival (PFS)
compared to fulvestrant alone in HR+/HER2- advanced breast cancer
patients with a PIK3CA mutation (median PFS 11.0 months vs 5.7 months;
Hazard Ratio (HR)=0.65, 95% CI: 0.50-0.85; p<0.001).2 Piqray
provided consistent PFS results across pre-specified subgroups,
including among patients previously treated with a CDK4/6 inhibitor.2
The
overall response rate (ORR), an indicator of the proportion of patients
who experience at least a 30% reduction in overall tumor size (in
patients with measurable disease), was more than doubled when Piqray was
added to fulvestrant in patients with a PIK3CA mutation, (ORR = 35.7%
vs 16.2% for fulvestrant alone, p=0.0002).2,3
Patients with HR+/HER2- advanced breast cancer should be selected for treatment with Piqray, based on the presence of a PIK3CA mutation in tumor tissue or plasma specimens, using a validated test. If a mutation is not detected in a plasma specimen, tumor tissue should be tested if available.1
"The PIK3CA gene is frequently mutated in HR+/HER2- breast cancer, affecting about 30% to 40% of people with that subtype 2. Advanced breast cancer patients with the PIK3CA mutations tend to have worse prognosis, developing resistance to standard treatment options more quickly.6,8,9,10," said Associate Prof Yap Yoon Sim, Senior Consultant, Division of Medical Oncology, National Cancer Centre Singapore.
In
Singapore, a total of 9,634 new cases of breast cancer cases were
diagnosed between 2011 -- 2015, accounting for nearly 1 in 3 incident
cancers in females and making it the most common cancer diagnosis among
women. Of which, 1 in 10 women diagnosed with breast cancer are of
advanced stages.7 The incidence of point mutations in PIK3CA,
are amongst the most frequently reported to date for any gene in breast
cancer in Singapore.4
Approximately 30-40% of those with HR+/HER2- subtype of breast cancer have a PIK3CA mutation2. PIK3CA mutations are associated with tumor growth, resistance to endocrine treatment and a poor overall prognosis.6,8,9,10 Piqray targets the effect of PIK3CA mutations and may help overcome endocrine resistance in HR+ advanced breast cancer.
PIQRAY
is the first drug of its kind approved for treatment of postmenopausal
women, and men, with hormone receptor positive, HER2- negative, advanced
breast cancer with a PIK3CA mutation in Singapore, the European Union,
and the United States.
About Piqray® (alpelisib)
Piqray
is a kinase inhibitor approved in combination with fulvestrant for the
treatment of postmenopausal women, and men, with HR+/HER2-,
PIK3CA-mutated, advanced or metastatic breast cancer, as detected by an
FDA-approved test following progression on or after endocrine-based
regimen.1
Approximately 30-40% of HR+ advanced
breast cancer patients have a mutation that may activate the PI3K-alpha
isoform, called PIK3CA mutations.2 These mutations are associated with resistance to endocrine therapy, disease progression and a poor prognosis.6,8,9,10 Piqray works by inhibiting the PI3K pathway, predominantly the PI3K-alpha isoform, to address the effect of PIK3CA mutations.
About SOLAR-1
SOLAR-1
is a global, Phase III randomized, double-blind, placebo-controlled
trial studying Piqray in combination with fulvestrant for postmenopausal
women, and men, 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 2,3. SOLAR-1 is the pivotal Phase III trial that supported this approval.
The
trial randomized 572 patients. Patients were allocated based on central
tumor tissue assessment to either a PIK3CA-mutated cohort (n=341) or a
PIK3CA non-mutated cohort (n=231). Within each cohort, patients were
randomized in a 1:1 ratio to receive continuous oral treatment with
Piqray (300 mg 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 treatment2,3. Patients and investigators are blinded to PIK3CA mutation status and treatment.
The
primary endpoint is local investigator assessed PFS using RECIST 1.1
for patients with a PIK3CA mutation. The key secondary endpoint is
overall survival, and additional secondary endpoints include, but are
not limited to, overall response rate, clinical benefit rate,
health-related quality of life, efficacy in PIK3CA non-mutated cohort,
safety and tolerability2. SOLAR-1 is ongoing to assess overall survival
and other secondary endpoints.
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.
Indication 1
Piqray is an α-specific class I phosphatidylinositol-3-kinase (PIK3CA) inhibitor indicated for the treatment of postmenopausal women, and men, with hormone receptor positive, HER2- negative, advanced breast cancer with a PIK3CA mutation in combination with fulvestrant after disease progression following an endocrine-based regimen.
Important Safety Information 1
Treatment with Piqray should be initiated by a physician experienced in the use of anticancer therapies.
Piqray
is contraindicated in patients with hypersensitivity to the active
substance or to any of the excipients. PIQRAY may cause serious side
effects. PIQRAY can cause hypersensitivity (including anaphylactic
reaction), manifested by symptoms including, but not limited to,
dyspnea, flushing, rash, fever or tachycardia.
The most common adverse drug reactions in Piqray plus fulvestrant treated patients were hyperglycaemia, diarrhea, rash, nausea, fatigue and asthenia, decreased appetite, stomatitis, vomiting and weight decreased.
Patients
should tell their health care provider all of the medicines they take,
including prescription and over-the-counter medicines, vitamins, and
herbal supplements. PIQRAY and other medicines may affect each other
causing side effects.
For more information, please see full Prescribing Information for Piqray, available at
https://www.novartis.com.sg/product-list/PIQRAY
*HSA approval for PIQRAY on 25th March 2020
References