> FDA Approves Alpelisib, First PI3K Inhibitor for Breast Cancer

FDA Approves Alpelisib, First PI3K Inhibitor for Breast Cancer


The targeted therapy offers a new treatment option for some hormone receptor-positive, HER2-negative advanced breast cancers

The Food and Drug Administration approved the targeted therapy alpelisib (Piqray) to treat certain hormone receptor-positive, HER2-negative breast cancers in postmenopausal women and in men. It is given with the hormonal therapy fulvestrant (Faslodex) to treat advanced and metastatic breast cancers that also have a mutation on the PIK3CA gene.

Alpelisib is the first PI3K inhibitor approved for breast cancer. The maker of the medicine, Novartis, announced the approval on May 24. The approval is based on the results of the SOLAR-1 trial, which Living Beyond Breast Cancer covered at the 2018 San Antonio Breast Cancer Symposium.


Alpelisib is a targeted therapy called a PI3K (phosphatidylinositol-3 kinase) inhibitor. These medicines work by blocking the PI3K pathway in cancer cells, which research suggests may make cancer less likely to respond to treatment with hormonal therapy. About 40 percent of people with hormone receptor-positive breast cancer have tumors that carry a PIK3CA mutation. The mutation can make the PI3K pathway too active and encourage the cancer to grow or spread, or to stop responding to hormonal therapy.

Past studies of PI3K inhibitors resulted in participants experiencing too many side effects. But a phase I study of alpelisib published in early 2017 suggested the medicine would be both safe and effective. It led to further research, including the SOLAR-1 trial on which the FDA approval is based.

The Approval

Alpelisib and a biomarker test, also sometimes called a genomic test, used to check for PIK3CA mutations were approved together. The test is called the therascreenPIK3CA Kit and is made by the company QIAGEN. The medicine and test are the first combination approved by the FDA through the Real-Time Oncology Review Pilot Program.

The FDA created the Real-Time Oncology Review Pilot Program to approve new treatments faster while ensuring the treatments are safe, as well.

The pilot program is similar to FDA’s existing breakthrough therapy designation, which helps medicines move through the approval process and get to the people who need them more quickly. The agency hopes it will help them find ways to streamline the review and approval process even more.

The SOLAR-1 Trial

SOLAR-1 was a phase III, randomized, double-blind trial. In randomized trials, a computer randomly assigns participants to treatment groups, rather than a doctor. In double-blind trials, neither the participants nor the research team know which treatment each participant receives.


SOLAR-1 enrolled 527 postmenopausal women and men who had

  • hormone receptor-positive, HER2-negative metastatic breast cancer
  • cancer return or spread to distant areas of the body, like the liver, lungs, bones or brain, during or after treatment with aromatase inhibitors for early-stage or metastatic disease

Participants were put into two trial groups

  • 341 people had breast cancers with PIK3CA mutations
  • 231 people had breast cancers without PIK3CA mutations

The participants in each group were randomly assigned to receive

  • alpelisib plus fulvestrant, or
  • a placebo, an inactive pill, plus fulvestrant

Alpelisib was given as a pill, and the daily dose was 300 milligrams.


The researchers looked at progression-free survival, the length of time from the start of treatment until the cancer grows or spreads, in both groups. They compared the progression-free survival of the participants who took alpelisib to the participants who took the placebo.

The research team found that the median progression-free survival was almost twice as long for people taking alpelisib. It was

  • 11.0 months in the alpelisib plus fulvestrant group
  • 5.7 months in the placebo plus fulvestrant group

More people taking alpelisib had the breast cancer shrink or disappear than people taking the placebo. In the trial,

  • 35.7 percent of people taking alpelisib plus fulvestrant had the cancer shrink or disappear
  • 16.2 percent of people taking the placebo plus fulvestrant had the cancer shrink or disappear

The researchers also looked at how well alpelisib works for breast cancer that doesn’t have a PIK3CA mutation. The results showed that adding alpelisib to fulvestrant didn’t treat cancers without a mutation much better than fulvestrant by itself. The progression-free survival was similar between the groups, so alpelisib only seems to help treat the cancer if it has a PIK3CA mutation.

SOLAR-1 continues to watch participants to see how alpelisib will impact overall survival, how long participants live after they start the study treatment.

Side Effects of Alpelisib

Alpelisib plus fulvestrant caused a variety of side effects in the people who took it. The most common side effects include

More people taking alpelisib plus fulvestrant stopped treatment due to side effects than did people taking the placebo plus fulvestrant. In the alpelisib group, 25 percent stopped treatment; in the placebo group, only 4.2 percent stopped. The most common reason participants stopped taking alpelisib was high blood sugar.

Most side effects were managed by lowering the dose of alpelisib. They were also managed by stopping treatment with alpelisib for a short period of time and starting it again later, once the side effects came more manageable or gone away.

What This Means for You

Alpelisib’s approval may give you a new treatment option if you have cancer that comes back or spreads during or after treatment with hormonal therapy.

To find out if alpelisib is right for you, you’ll need biomarker testing, with the therascreenPIK3CA Kit as one of the tests available. The test will look at a sample of tumor tissue or a blood sample to see if the cancer has a PIK3CA mutation. There are several biomarker tests available that test for different mutations in cancer.

The current price for alpelisib, without insurance, is $15,000 per month. If you have insurance, the cost to you can vary based on how much your insurance pays for treatment. Novartis also has financial assistance plans to help you pay for your medicine if you need it.

The most common and the most serious reported in SOLAR-1 was high blood sugar. PI3K inhibitors can cause high blood sugar because the PI3K pathway helps the body control insulin, a hormone that helps control your blood sugar when your body processes food. If you develop high blood sugar, you may be able to manage it with medicine. Your doctor will test your blood sugar before you start alpelisib and keep an eye on it as you go through treatment.

If you have diabetes, you may worry that alpelisib could impact your blood sugar and insulin levels, or wonder if you can take it. The FDA approval allows people with diabetes to take alpelisib. Your doctor should pay very close attention to your blood sugar while you are taking the medicine. If you have concerns, share them with your care team.


Fabrice, A, Ciruelos, E, Rubovszky, G, et al. Alpelisib for PIK3CA-Mutated, Hormone Receptor–Positive Advanced Breast Cancer. New England Journal of Medicine. May 16, 2019; 380:1929-1940. DOI: 10.1056/NEJMoa1813904.