Alpelisib

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Alpelisib
Alpelisib.svg
Clinical data
Trade names Piqray, Vijoice
Other namesBYL719
AHFS/Drugs.com Monograph
MedlinePlus a619036
License data
Pregnancy
category
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
Identifiers
  • (2S)-1-N-[4-Methyl-5-[2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl]-1,3-thiazol-2-yl]pyrrolidine-1,2-dicarboxamide
CAS Number
PubChem CID
PubChemSID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.233.704 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C19H22F3N5O2S
Molar mass 441.47 g·mol−1
3D model (JSmol)
  • CC1=C(SC(=N1)NC(=O)N2CCCC2C(=O)N)C3=CC(=NC=C3)C(C)(C)C(F)(F)F
  • InChI=1S/C19H22F3N5O2S/c1-10-14(11-6-7-24-13(9-11)18(2,3)19(20,21)22)30-16(25-10)26-17(29)27-8-4-5-12(27)15(23)28/h6-7,9,12H,4-5,8H2,1-3H3,(H2,23,28)(H,25,26,29)/t12-/m0/s1
  • Key:STUWGJZDJHPWGZ-LBPRGKRZSA-N

Alpelisib, sold under the brand name Piqray among others, is a medication used to treat certain types of breast cancer. [8] It is used together with fulvestrant. [8] It is taken by mouth. [8] It is marketed by Novartis. [8]

Contents

Common side effects include high blood sugar, kidney problems, diarrhea, rash, low blood cells, liver problems, pancreatitis, vomiting, and hair loss. [8] It is an alpha-specific PI3K inhibitor. [8] [9] It was approved for medical use in the United States in May 2019. [8] [10]

Medical uses

Alpelisib is indicated 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, PIK3CA-mutated, advanced or metastatic breast cancer as detected by an FDA-approved test following progression on or after an endocrine-based regimen. [11]

In the European Union, alpelisib is indicated 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. [6]

In April 2022, the indication for alpelisib was expanded in the US to include the treatment of severe manifestations of PIK3CA-related overgrowth spectrum (PROS) in those who require systemic therapy. [5] [12] [13]

History

In May 2019, alpelisib was approved in the United States for use in combination with the endocrine therapy fulvestrant, to treat postmenopausal women, and men, with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, advanced or metastatic breast cancer following progression on or after an endocrine-based regimen. [8] [4] [10]

The U.S. Food and Drug Administration (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. [8]

The efficacy of alpelisib was studied in the SOLAR-1 trial (NCT02437318), a randomized trial of 572 postmenopausal women and men with HR-positive, HER2-negative, advanced or metastatic breast cancer whose cancer had progressed while on or after receiving an aromatase inhibitor. [8] [14]

The FDA granted the application for alpelisib priority review designation and granted approval of Piqray to Novartis. [8] The FDA granted approval of the therascreen PIK3CA RGQ PCR Kit to Qiagen Manchester, Ltd. [8]

On 28 May 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product alpelisib (Piqray), intended for the treatment of locally advanced or metastatic breast cancer with a PIK3CA mutation. [6] The applicant for this medicinal product is Novartis Europharm Limited. [6] Alpelisib was approved for medical use in the European Union in July 2020. [6]

Society and culture

Alpelisib was approved for medical use in the United States in May 2019, [8] [10] in Australia in March 2020, [15] and in the European Union in July 2020. [6]

Related Research Articles

Fulvestrant, sold under the brand name Faslodex among others, is an antiestrogenic medication used to treat hormone receptor (HR)-positive metastatic breast cancer in postmenopausal women with disease progression as well as HR-positive, HER2-negative advanced breast cancer in combination with abemaciclib or palbociclib in women with disease progression after endocrine therapy. It is given by injection into a muscle.

<span class="mw-page-title-main">Lapatinib</span> Cancer medication

Lapatinib (INN), used in the form of lapatinib ditosylate (USAN) is an orally active drug for breast cancer and other solid tumours. It is a dual tyrosine kinase inhibitor which interrupts the HER2/neu and epidermal growth factor receptor (EGFR) pathways. It is used in combination therapy for HER2-positive breast cancer. It is used for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 (ErbB2).

<span class="mw-page-title-main">Olaparib</span> Chemical compound (cancer therapy drug)

Olaparib, sold under the brand name Lynparza, is a medication for the maintenance treatment of BRCA-mutated advanced ovarian cancer in adults. It is a PARP inhibitor, inhibiting poly ADP ribose polymerase (PARP), an enzyme involved in DNA repair. It acts against cancers in people with hereditary BRCA1 or BRCA2 mutations, which include some ovarian, breast, and prostate cancers.

<span class="mw-page-title-main">Phosphoinositide 3-kinase inhibitor</span>

Phosphoinositide 3-kinase inhibitors are a class of medical drugs that are mainly used to treat advanced cancers. They function by inhibiting one or more of the phosphoinositide 3-kinase (PI3K) enzymes, which are part of the PI3K/AKT/mTOR pathway. This signal pathway regulates cellular functions such as growth and survival. It is strictly regulated in healthy cells, but is always active in many cancer cells, allowing the cancer cells to better survive and multiply. PI3K inhibitors block the PI3K/AKT/mTOR pathway and thus slow down cancer growth. They are examples of a targeted therapy. While PI3K inhibitors are an effective treatment, they can have very severe side effects and are therefore only used if other treatments have failed or are not suitable.

A CDK inhibitor is any chemical that inhibits the function of CDKs. They are used to treat cancers by preventing overproliferation of cancer cells. The US FDA approved the first drug of this type, palbociclib (Ibrance), a CDK4/6 inhibitor, in February 2015, for use in postmenopausal women with breast cancer that is estrogen receptor positive and HER2 negative. While there are multiple cyclin/CDK complexes regulating the cell cycle, CDK inhibitors targeting CDK4/6 have been the most successful; four CDK4/6 inhibitors have been FDA approved. No inhibitors targeting other CDKs have been FDA approved, but several compounds are in clinical trials.

<span class="mw-page-title-main">Trastuzumab emtansine</span> Pharmaceutical drug

Trastuzumab emtansine, sold under the brand name Kadcyla, is an antibody-drug conjugate consisting of the humanized monoclonal antibody trastuzumab (Herceptin) covalently linked to the cytotoxic agent DM1. Trastuzumab alone stops growth of cancer cells by binding to the HER2 receptor, whereas trastuzumab emtansine undergoes receptor-mediated internalization into cells, is catabolized in lysosomes where DM1-containing catabolites are released and subsequently bind tubulin to cause mitotic arrest and cell death. Trastuzumab binding to HER2 prevents homodimerization or heterodimerization (HER2/HER3) of the receptor, ultimately inhibiting the activation of MAPK and PI3K/AKT cellular signalling pathways. Because the monoclonal antibody targets HER2, and HER2 is only over-expressed in cancer cells, the conjugate delivers the cytotoxic agent DM1 specifically to tumor cells. The conjugate is abbreviated T-DM1.

<span class="mw-page-title-main">Palbociclib</span> Medication for HR+ HER2− breast cancer

Palbociclib, sold under the brand name Ibrance among others, is a medication developed by Pfizer for the treatment of HR-positive and HER2-negative breast cancer. It is a selective inhibitor of the cyclin-dependent kinases CDK4 and CDK6. Palbociclib was the first CDK4/6 inhibitor to be approved as a cancer therapy.

<span class="mw-page-title-main">Sacituzumab govitecan</span> Antibody-drug conjugate

Sacituzumab govitecan, sold under the brand name Trodelvy by Gilead Sciences, is a Trop-2-directed antibody and topoisomerase inhibitor drug conjugate used for the treatment of metastatic triple-negative breast cancer and metastatic urothelial cancer.

<span class="mw-page-title-main">Buparlisib</span> Chemical compound

Buparlisib is an experimental anti-cancer medication. It is a small molecule orally-available pan-class I phosphoinositide 3-kinase (PI3K) inhibitor. Buparlisib was under investigation as a treatment for advanced breast cancer but was abandoned due to negative results. It is still under investigation as a potential treatment for head and neck squamous cell carcinoma (HNSCC).

A selective estrogen receptor degrader or downregulator (SERD) is a type of drug which binds to the estrogen receptor (ER) and, in the process of doing so, causes the ER to be degraded and thus downregulated. They are used to treat estrogen receptor-sensitive or progesterone receptor-sensitive breast cancer, along with older classes of drugs like selective estrogen receptor modulators (SERMs) and aromatase inhibitors.

<span class="mw-page-title-main">Abemaciclib</span> Anti-breast cancer medication

Abemaciclib, sold under the brand name Verzenio among others, is a medication for the treatment of advanced or metastatic breast cancers. It was developed by Eli Lilly and it acts as a CDK inhibitor selective for CDK4 and CDK6.

<span class="mw-page-title-main">Ribociclib</span> Chemical compound

Ribociclib, sold under the brand name Kisqali, is a medication used for the treatment of certain kinds of breast cancer. Ribociclib is a kinase inhibitor. It was developed by Novartis and Astex Pharmaceuticals.

<span class="mw-page-title-main">Elacestrant</span> Chemical compound

Elacestrant, sold under the brand name Orserdu, is an anticancer medication which is used in the treatment of breast cancer. It is taken by mouth.

<span class="mw-page-title-main">Tucatinib</span> Chemical compound

Tucatinib, sold under the brand name Tukysa, is an anticancer medication used for the treatment of HER2-positive breast cancer. It is a small molecule inhibitor of HER2. It was developed by Array BioPharma and licensed to Cascadian Therapeutics.

<span class="mw-page-title-main">Trastuzumab deruxtecan</span> Medication

Trastuzumab deruxtecan, sold under the brand name Enhertu, is an antibody-drug conjugate consisting of the humanized monoclonal antibody trastuzumab (Herceptin) covalently linked to the topoisomerase I inhibitor deruxtecan. It is licensed for the treatment of breast cancer or gastric or gastroesophageal adenocarcinoma. Trastuzumab binds to and blocks signaling through epidermal growth factor receptor 2 (HER2/neu) on cancers that rely on it for growth. Additionally, once bound to HER2 receptors, the antibody is internalized by the cell, carrying the bound deruxtecan along with it, where it interferes with the cell's ability to make DNA structural changes and replicate its DNA during cell division, leading to DNA damage when the cell attempts to replicate itself, destroying the cell.

Pertuzumab/trastuzumab/hyaluronidase, sold under the brand name Phesgo, is a fixed-dose combination medication to treat adults with HER2-positive breast cancer that has spread to other parts of the body, and for treatment of adults with early HER2-positive breast cancer. It contains pertuzumab, trastuzumab, and hyaluronidase–zzxf. It is injected under the skin via subcutaneous injection in the thigh. In the European Union, Phesgo contains the active ingredients pertuzumab and trastuzumab along with the enzyme vorhyaluronidase alfa.

Trastuzumab/hyaluronidase, sold under the brand name Herceptin SC among others, is a fixed-dose combination medication for the treatment of HER2-overexpressing breast cancer in adults. It is a combination of trastuzumab and hyaluronidase.

Endocrine therapy is a common treatment for estrogen receptor positive breast cancer. However, resistance to this therapy can develop, leading to relapse and progression of disease. This highlights the need for new strategies to combat this resistance.

<span class="mw-page-title-main">Inavolisib</span> Chemical compound

Inavolisib, or GDC-0077, is an investigational, highly selective inhibitor and degrader of mutant phosphatidylinositol 3-kinase (PI3K) alpha. The PI3K-mediated signalling pathway has shown to play an important role in the development of tumours as dysregulation is commonly associated with tumour growth and resistance to antineoplastic agents and radiotherapy.

<span class="mw-page-title-main">Capivasertib</span> Medication

Capivasertib, sold under the brand name Truqap, is an anti-cancer medication used for the treatment of breast cancer. It is taken by mouth.

References

  1. 1 2 "Piqray Australian prescription medicine decision summary". Therapeutic Goods Administration (TGA). 27 March 2020. Archived from the original on 27 August 2021. Retrieved 16 August 2020.
  2. ↑ "Updates to the Prescribing Medicines in Pregnancy database". Therapeutic Goods Administration (TGA). 12 May 2022. Archived from the original on 3 April 2022. Retrieved 13 May 2022.
  3. ↑ "Summary Basis of Decision (SBD) for Piqray". Health Canada. 23 October 2014. Archived from the original on 30 May 2022. Retrieved 29 May 2022.
  4. 1 2 "Piqray- alpelisib tablet Piqray- alpelisib kit". DailyMed. 12 June 2020. Archived from the original on 28 October 2020. Retrieved 16 August 2020.
  5. 1 2 "Vijoice- alpelisib tablet Vijoice- alpelisib kit". DailyMed. 7 April 2022. Archived from the original on 28 April 2022. Retrieved 27 April 2022.
  6. 1 2 3 4 5 6 "Piqray EPAR". European Medicines Agency (EMA). 26 May 2020. Archived from the original on 14 August 2020. Retrieved 16 August 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  7. ↑ "Piqray Product information". Union Register of medicinal products. Retrieved 3 March 2023.
  8. 1 2 3 4 5 6 7 8 9 10 11 12 13 "FDA approves first PI3K inhibitor for breast cancer". U.S. Food and Drug Administration (FDA) (Press release). 24 May 2019. Archived from the original on 25 November 2019. Retrieved 29 May 2019.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  9. ↑ André F, Ciruelos E, Rubovszky G, Campone M, Loibl S, Rugo HS, et al. (May 2019). "PIK3CA-Mutated, Hormone Receptor-Positive Advanced Breast Cancer". The New England Journal of Medicine. 380 (20): 1929–1940. doi: 10.1056/NEJMoa1813904 . hdl: 11577/3308753 . PMID   31091374.
  10. 1 2 3 "Drug Approval Package: Piqray". U.S. Food and Drug Administration (FDA). 18 June 2019. Archived from the original on 25 November 2019. Retrieved 25 November 2019.
  11. ↑ "Piqray (alpelisib) tablets HR+/HER2- Advanced Breast Cancer Treatment". Novartis. Archived from the original on 24 August 2021. Retrieved 24 August 2021.
  12. ↑ "FDA approves alpelisib for PIK3CA-related overgrowth spectrum". U.S. Food and Drug Administration (FDA). 6 April 2022. Archived from the original on 7 April 2022. Retrieved 8 April 2022.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  13. ↑ "FDA approves Novartis Vijoice (alpelisib) as first and only treatment for select patients with PIK3CA-Related Overgrowth Spectrum (PROS)". Novartis (Press release). 6 April 2022. Archived from the original on 6 April 2022. Retrieved 9 April 2022.
  14. ↑ "Drug Trials Snapshots: Piqray". U.S. Food and Drug Administration (FDA). 14 June 2019. Archived from the original on 25 November 2019. Retrieved 24 November 2019.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  15. ↑ "AusPAR: Alpelisib". Therapeutic Goods Administration (TGA). 3 September 2020. Archived from the original on 27 October 2020. Retrieved 23 September 2020.
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