Alpelisib/Fulvestrant Combination Wins Philippine Approval for PIK3CA-Mutated, HR+/HER2– Metastatic Breast Cancer

The Philippine FDA has granted approval to alpelisib in combination with fulvestrant for the treatment of patients with PIK3CA-mutated, HR-positive, HER2-negative advanced or metastatic breast cancer.

The Philippine FDA has granted approval to alpelisib (Vijoice) in combination with fulvestrant (Faslodex) for the treatment of patients with PIK3CA-mutated, hormone receptor (HR)–positive, HER2-negative advanced or metastatic breast cancer who have disease progression following an endocrine-containing regimen.1

The approval is based on findings from the phase 3 SOLAR-1 trial (NCT02437318), which showed alpelisib plus fulvestrant prolonged progression-free survival (PFS) compared with placebo plus fulvestrant in patients with HR-positive/HER2-negative breast cancer harboring PIK3CA mutations who had previously progressed on endocrine therapy.2

At a median follow-up of 20 months, alpelisib/fulvestrant elicited an investigator-assessed median PFS of 11.0 months (95% CI, 7.5-14.5) in a cohort of patients with PIK3CA-mutated disease compared with 5.7 months (95% CI, 3.7-7.4) in the placebo arm (HR, 0.65; 95% CI, 0.50-0.85; P < .001).

“[Alpelisib] is the first-ever treatment specifically for HR-positive/HER2-negative advanced breast cancer with a PIK3CA mutation. We are pleased to bring to the Philippines a new treatment option that specifically addresses the needs of the patients living with this mutation,” Joel Chong, the country president of Novartis Healthcare Philippines, stated in a press release.

In May 2019, the U.S. FDA approved alpelisib plus fulvestrant as a treatment for postmenopausal women, and men, with HR-positive, HER2-negative, PIK3CA-mutated, advanced or metastatic breast cancer following progression on or after an endocrine-based regimen, also based on findings from SOLAR-1.3

The multicenter trial enrolled patients with a histologically and/or cytologically confirmed diagnosis of HR-positive, HER2-negative advanced breast cancer who had an identified PIK3CA status who relapsed during or following prior endocrine therapy. Patients were excluded if they received prior treatment with fulvestrant or any PIK3, AKT, or mTOR inhibitor.

Patients were randomly assigned to 300 mg of oral alpelisib or placebo once per day with 500 mg of intramuscular fulvestrant once every 28 days and on days 1 and 15 of cycle 1. In the cohort of patients harboring PIK3CA mutations, 169 and 172 patients were randomized to receive alpelisib or placebo, respectively.

Along with a primary end point of PFS per investigator assessment, key secondary end points included overall survival, overall response rate (ORR), and safety.

Among patients in the PIK3CA-mutated cohort, the median ages of alpelisib and placebo groups were 63 (range, 25-87) and 64 (range, 38-92), respectively. The majority of patients were female (99.4% and 100%, respectively), had an ECOG performance status of 0 (66.3% and 65.7%), had visceral metastases (55% and 58.1%), were in the first line of treatment for advanced disease (52.1% and 51.7%), and had secondary resistance to endocrine therapy (71% and 73.8%).

Additional data showed that the median PFS per blinded independent review committee assessment was 11.1 months (95% CI, 7.3-16.8) in the alpelisib arm vs 3.7 months (95% CI, 2.1-5.6) in the placebo arm (HR, 0.48; 95% CI, 0.32-0.71). Notably, in patients without PIK3CA-mutated disease, the median PFS was 7.4 months and 5.6 months in the alpelisib and placebo arms, respectively (HR, 0.85; 95% CI, 0.58-1.25).

In the PIK3CA-mutated cohort, the ORR was 26.6% in the alpelisib arm compared with 12.8% in the placebo arm (P = .0006).

Regarding safety for enrolled patients in both cohorts, the most common grade 3/4 adverse effects (AEs) included hyperglycemia (36.6% and 0.7% in the alpelisib and placebo groups, respectively) and rash (9.9% and 0.3%). Investigators observed grade 3 diarrhea in 6.7% of patients in the alpelisib arm compared with 0.3% in the placebo arm. AEs led to treatment discontinuation of 25% of patients in the alpelisib arm, compared with 4.2% in the placebo arm.

"The regulatory approval of alpelisib is a game changer in the way we practice medicine in advanced breast cancer. For the first time, physicians can test for PIK3CA biomarkers and develop a treatment plan based on the genomic profile of a patient's cancer," Arnold John B. Uson, MD, president of the Philippine Society of Medical Oncology, stated in a press release.


  1. Philippine FDA approves Novartis advanced breast cancer treatment, alpelisib. News release. Novartis. July 11, 2022. Accessed July 18, 2022.
  2. Andre F, Ciruelos E, Rubovszky G, et al. Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer. N Engl J Med. 2019;380(20):1929-1940. doi:10.1056/NEJMoa1813904
  3. FDA approves alpelisib for metastatic breast cancer. News release. FDA. May 24, 2019. Accessed July 17, 2022.