Buparlisib
Clinical data
Other namesAN2025, BKM120
ATC code
  • None
Identifiers
  • 5-[2,6-bis(morpholin-4-yl)pyrimidin-4-yl]-4-(trifluoromethyl)pyridin-2-amine
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
ECHA InfoCard100.232.248
Chemical and physical data
FormulaC18H21F3N6O2
Molar mass410.401 g·mol−1
3D model (JSmol)
  • NC1=NC=C(C2=CC(=NC(=N2)N2CCOCC2)N2CCOCC2)C(=C1)C(F)(F)F
  • InChI=1S/C18H21F3N6O2/c19-18(20,21)13-9-15(22)23-11-12(13)14-10-16(26-1-5-28-6-2-26)25-17(24-14)27-3-7-29-8-4-27/h9-11H,1-8H2,(H2,22,23) ☒N
  • Key:CWHUFRVAEUJCEF-UHFFFAOYSA-N ☒N

Buparlisib (codenamed AN2025 and BKM120) is an experimental anti-cancer medication. It is a small molecule orally-available pan-class I phosphoinositide 3-kinase (PI3K) inhibitor.[1] 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).

Clinical trials

Buparlisib was under investigation as a treatment for advanced or metastatic HER2-negative breast cancer in several phase III clinical trials:

  • The phase III trial BELLE-2 compared buparlisib + fulvestrant with fulvestrant alone in patients with advanced or metastatic HER2-negative, hormone receptor-positive (HR+) aromatase inhibitor-resistant breast cancer. Treatment with buparlisib prolonged progression-free survival (PFS) significantly but also resulted in excessive side effects.[2][3]
  • Similar to BELLE-2, the phase III trial BELLE-3 compared buparlisib + fulvestrant with fulvestrant alone in patients with advanced or metastatic HER2-negative breast cancer, however in this trial, the disease had to be resistant to a mammalian target of rapamycin (mTOR) inhibitor. The trial was terminated due to excessive side effects.[4][5]
  • The phase II/III trial BELLE-4 compared buparlisib + paclitaxel with paclitaxel alone in patients with advanced or metastatic HER2-negative breast cancer regardless of hormone receptor status. Addition of buparlisib to paclitaxel did not improve PFS, and the trial was stopped for futility at the end of phase II.[6][7]

These results led the trials' sponsor, Novartis, to cancel their breast cancer study program with buparlisib.

Buparlisib is still under investigation as a potential treatment for head and neck squamous cell carcinoma (HNSCC) in the ongoing phase III trial BURAN, which compares buparlisib + paclitaxel to paclitaxel alone in patients with recurrent or metastatic HNSCC. Results are expected for December 2022.[8]

References

  1. ↑ Geuna E, Milani A, Martinello R, Aversa C, Valabrega G, Scaltriti M, Montemurro F (March 2015). "Buparlisib , an oral pan-PI3K inhibitor for the treatment of breast cancer". Expert Opinion on Investigational Drugs. 24 (3): 421–431. doi:10.1517/13543784.2015.1008132. PMID 25645727. S2CID 40698715.
  2. ↑ Baselga J, Im SA, Iwata H, Cortés J, De Laurentiis M, Jiang Z, et al. (July 2017). "Buparlisib plus fulvestrant versus placebo plus fulvestrant in postmenopausal, hormone receptor-positive, HER2-negative, advanced breast cancer (BELLE-2): a randomised, double-blind, placebo-controlled, phase 3 trial". The Lancet. Oncology. 18 (7): 904–916. doi:10.1016/S1470-2045(17)30376-5. PMC 5549667. PMID 28576675.
  3. ↑ Clinical trial number NCT01610284 for "Phase III Study of BKM120/Placebo With Fulvestrant in Postmenopausal Patients With Hormone Receptor Positive HER2-negative Locally Advanced or Metastatic Breast Cancer Refractory to Aromatase Inhibitor (BELLE-2)" at ClinicalTrials.gov
  4. ↑ Di Leo A, Johnston S, Lee KS, Ciruelos E, Lønning PE, Janni W, et al. (January 2018). "Buparlisib plus fulvestrant in postmenopausal women with hormone-receptor-positive, HER2-negative, advanced breast cancer progressing on or after mTOR inhibition (BELLE-3): a randomised, double-blind, placebo-controlled, phase 3 trial". The Lancet. Oncology. 19 (1): 87–100. doi:10.1016/S1470-2045(17)30688-5. PMID 29223745.
  5. ↑ Clinical trial number NCT01633060 for "A Phase III Study of BKM120 With Fulvestrant in Patients With HR+,HER2-, AI Treated, Locally Advanced or Metastatic Breast Cancer Who Progressed on or After mTORi (BELLE-3)" at ClinicalTrials.gov
  6. ↑ Martín M, Chan A, Dirix L, O'Shaughnessy J, Hegg R, Manikhas A, et al. (February 2017). "A randomized adaptive phase II/III study of buparlisib, a pan-class I PI3K inhibitor, combined with paclitaxel for the treatment of HER2- advanced breast cancer (BELLE-4)". Annals of Oncology. 28 (2): 313–320. doi:10.1093/annonc/mdw562. PMID 27803006.
  7. ↑ Clinical trial number NCT01572727 for "A Study of the Experimental Drug BKM120 With Paclitaxel in Patients With HER2 Negative, Locally Advanced or Metastatic Breast Cancer, With or Without PI3K Activation (BELLE-4)" at ClinicalTrials.gov
  8. ↑ Clinical trial number NCT04338399 for "The BURAN Study of Buparlisib in Patients With Recurrent or Metastatic HNSCC (BURAN)" at ClinicalTrials.gov
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