New Medicines

Piqray · Breast cancer; advanced or metastatic hormone receptor positive (HR+), HER2-negative, PIK3CA-mutated in men and postmenopausal women - second-line with fulvestrant


New molecular entity

Development and Regulatory status

Pre-registration (Filed)
Pre-registration (Filed)

May 19: The 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 19: US 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 19: Is also pre-registration in the US [11].

Feb 19: Filed in EU [10].

Dec 17: Filings planned for 2018 [6].

Mar 17: Novartis remains on course to file in 2019 [5].

Dec 15: Filings planned for 2019 [1].


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].
Breast cancer; advanced or metastatic hormone receptor positive (HR+), HER2-negative, PIK3CA-mutated in men and postmenopausal women - second-line with fulvestrant

Further information

December 2020

Trial or other data

May 19: Results 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 18: Novartis 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].

Oct 18: Details 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]

Aug 18: SOLAR-1 study meets it´s primary endpoint showing an improvement in progression free survival [7].

Dec 16: NCT02437318 initial results due July 2019 [4]

Jul 15: PIII 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