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38924711000001103

New Medicines

PiqrayHR-positive, HER2-negative, PIK3CA-mutated breast cancer - second-line with fulvestrant after endocrine monotherapy

Information

Piqray
New molecular entity
Novartis
Novartis

Development and Regulatory status

Launched
Launched
Launched
September 2020
Sep 20Launched in the UK. Price: 50mg x 28 and 200mg x 28=£4082.14; 150mg x 56=£4082.14; 200mg x, 28=£4082.14 [16].
May 20Recommended for EU approval by CHMP - the full indication is "in combination with fulvestrant for the treatment of postmenopausal women, and men, with hormone receptor (HR)‑positive, human epidermal growth factor receptor 2 (HER2)‑negative, locally advanced or metastatic breast cancer with a PIK3CA mutation after disease progression following endocrine therapy as monotherapy." It is proposed that the medicine be prescribed by physicians experienced in the use of cancer treatments. [15]
May 19The FDA also approved the companion diagnostic test, therascreen PIK3CA RGQ PCR Kit, to detect the PIK3CA mutation in a tissue and/or a liquid biopsy. Patients who are negative by the therascreen test using the liquid biopsy should undergo tumour biopsy for PIK3CA mutation testing. Novartis has already launched Piqray with a list price of $15,500 for a 28-day supply [14].
May 19US FDA approved alpelisib in combination with fulvestrant (and its companion diagnostic test) for treatment of postmenopausal women, and men, with hormone receptor-positive, human epidermal growth factor receptor-2 negative (HR+/HER2-), PIK3CA-mutated, advanced or metastatic breast cancer [13].
Feb 19Is also pre-registration in the US [11].
Feb 19Filed in EU [10].
Dec 17Filings planned for 2018 [6].
Mar 17Novartis remains on course to file in 2019 [5].
Dec 15Filings planned for 2019 [1].

Category

Phosphoinositide 3-kinase (P13K) alfa inhibitor
Approximately 80% of breast cancers in postmenopausal women are HR+. Approx 70–80% of people with metastatic breast cancer have HER2- tumours, of which about 50% will also be HR+. Both HR+ and HER2- breast cancers are associated with a better prognosis than HR- and HER2+ disease. PIK3CA mutations account for 40% of all HR+/HER2- breast cancer cases and are associated with poor disease prognosis [3,14].
HR-positive, HER2-negative, PIK3CA-mutated breast cancer - second-line with fulvestrant after endocrine monotherapy
Oral

Further information

Yes
Suspended

Trial or other data

May 19Results of PIII SOLAR-1 RCT (n=572; NCT02437318) are published; at a median follow-up of 20 months, treatment with alpelisib, in combination with fulvestrant (FV) prolonged progression-free survival vs. FV in patients with PIK3CA-mutated cancer (11.0 vs. 5.7 months; HR 0.65; 95% CI,0.50-0.85; p<0.001) [12].
Oct 18Details of positive data from SOLAR-1 (n=572) posted by company. In HR+ advanced breast cancer pts with a PIK3CA mutation, progression free survival (PFS) was 11 months for alpelisib plus fulvestrant vs. 5.7 months for fulvestrant alone. The objective response rate (ORR) showed a reduction in tumour size of ~36% vs. 16% on fulvestrant alone but the PFS improvement was not seen in patients without the PIK3CA mutation. The most common all-grade adverse effects were hyperglycemia (64% vs 10%), diarrhoea (58% vs. 16%), nausea (45% vs. 22%), decreased appetite (36% vs. 11%) and rash (36% vs. 6%). Hyperglycemia was the most common grade 3/4 events (37% against <1%) [8].
Oct 18Novartis initiates an expanded access study to allow access to alpelisib for eligible patients with hormone receptor positive, advanced or metastatic breast cancer harboring a PIK3CA mutation (NCT03706573) [9].
Aug 18SOLAR-1 study meets it´s primary endpoint showing an improvement in progression free survival [7].
Dec 16NCT02437318 initial results due July 2019 [4].
Jul 15PIII SOLAR-1 study (NCT02437318) to determine whether treatment with alpelisib plus fulvestrant prolongs progression-free survival compared to fulvestrant and placebo in men and postmenopausal women with hormone receptor positive (HR+), HER2-negative advanced breast cancer, who received prior treatment with an Aromatase Inhibitor either as (neo)adjuvant or for advanced disease starts. 820 adults will be recruited in the US, Austria, Belgium, Canada, Czech Republic, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Japan, Republic of Korea, Lebanon, Netherlands, Spain, Sweden, Taiwan & Thailand. Collection of primary outcome data should complete Jul 19 [2].

Evidence based evaluations

Piqray HR-positive, HER2-negative, PIK3CA-mutated breast cancer - second-line with fulvestrant after CDK-4/6 inhibitor plus an aromatase inhibitor

Information

Piqray
Licence extension / variation
Novartis
Novartis

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

Phosphoinositide 3-kinase (PI3K) alfa inhibitor
Approximately 80% of breast cancers in postmenopausal women are HR+. Approx 70–80% of people with metastatic breast cancer have HER2- tumours, of which about 50% will also be HR+. Both HR+ and HER2- breast cancers are associated with a better prognosis than HR- and HER2+ disease. PIK3CA mutations account for 40% of all HR+/HER2- breast cancer cases and are associated with poor disease prognosis [1,2].
HR-positive, HER2-negative, PIK3CA-mutated breast cancer - second-line with fulvestrant after CDK-4/6 inhibitor plus an aromatase inhibitor
Oral

Further information

Yes
March 2022

Evidence based evaluations

Piqray Advanced triple negative breast cancer, with a PIK3CA mutation - in combination with Abraxane

Information

Piqray
Licence extension / variation
Novartis
Novartis

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

Phosphoinositide 3-kinase (PI3K) alfa inhibitor. Dosed 300 mg once daily. Abraxane dosed at 100 mg/m² by IV infusion on days 1, 8 and 15 of a 28-day cycle.
There are around 55,200 new breast cancer cases in the UK every year. Around 15 out of every 100 breast cancers (15%) are triple negative [1].
Advanced triple negative breast cancer, with a PIK3CA mutation - in combination with Abraxane
Oral