PI3k inhibitor, Alpelisib

            The following article was adapted from the website of Living Beyond Breast Cancer (LBBC). This is an organization based in Philadelphia, therefore it describes the US situation. This drug received approval from FDA in May 2019. Its mechanism of action is very different from the CDK4/6 inhibitors or PARP inhibitors.  For more details, ask your oncologist.  




AUGUST 16, 2019


Adam Brufsky, MD, PhD

            Alpelisib (Piqray) is a targeted therapy approved by the U.S. Food and Drug Administration to treat people with advanced, or metastatichormone receptor-positive breast cancer that has tested positive for a mutation on the PIK3CA gene. It is a PI3K (phosphatidylinositol-3 kinase) inhibitor,  a type of medicine that works by blocking a pathway  called PI3K. If this pathway becomes hyperactive in the tumor, then the cells do not respond to hormone inhibition anymore.  Alpelisib is given with the hormonal therapy fulvestrant (Faslodex).

            Alpelisib was approved by the FDA in May 2019 and is the first PI3K inhibitor approved to treat breast cancer. 

How Alpelisib Works

As the cancer grows the cells accumulate mutations. Some of them may make the cells grow faster, that is cells with such mutations are selected for and predominate. That is, the mutation exists in the cancer cells only, it is not inherited.  One such mutation is on a gene called PIK3CA and it can cause the PI3K pathway in the breast cancer cells to become too active. This pathway causes some breast cancer cells to stop responding to hormonal therapy, ie the anti-estrogen drugs (tamoxiphen or Letrozole) do not stop their division.  Alpelisib is a PI3K inhibitor, meaning it blocks this pathway and works with hormonal therapy to keep the cancer from growing.

Who Gets Alpelisib

Alpelisib is approved for people with advanced or metastatichormone receptor-positive, HER2-negative breast cancer that has grown during or after treatment with hormonal therapy. The tumor must also test positive for a mutation on the PIK3CA gene. This mutation is present in the tumors of about 40 percent of people with this diagnosis. Along with alpelisib, the FDA approved a biomarker test, the therascreenPIK3CA RGQ PCR kit, to test for this mutation.

How Alpelisib is given

Alpelisib is a pill. The standard dose is two 150 milligram tablets each day. It is given along with fulvestrant, which is given as a shot. Fulvestrant is given three times the first month, then once a month after that.

Side Effects and Things to Remember

High blood sugar is a notable side effect of alpelisib. In the SOLAR-1 trial it was the most common reason people stopped treatment with alpelisib. It can be managed with diabetes medicines (eg metformin), changes in diet, changes to the dose of alpelisib, and taking a break from alpelisib.

Other common side effects were:

Tell your doctor if you are pregnant or planning to become pregnant. Alpelisib may be dangerous to a fetus so it is recommended that you not take this medicine while pregnant and not get pregnant for at least a week after you have stopped treatment.

Alpelisib can also cause some serious but rare conditions including lung inflammation, allergic reactions, and severe skin reactions. Let your doctor know if you have had any serious skin reactions to medicines in the past.

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