Alpelisib Efficacy without Cherry-PI3King Mutations

Clin Cancer Res. 2023 Mar 14;29(6):989-990. doi: 10.1158/1078-0432.CCR-22-3411.


The PI3K inhibitor alpelisib is clinically approved for the treatment of metastatic estrogen receptor-positive breast cancers harboring hotspot mutations in PIK3CA, which encodes a subunit of PI3K. Prospective clinical trial results demonstrated benefit from alpelisib for the treatment of advanced ER+ breast cancers harboring PIK3CA mutations in the hotspots of exons 7, 9, and 20. However, 20% of PIK3CA mutations occur in non-hotspot regions. A recent article demonstrated that patients with cancers bearing non-hotspot PIK3CA mutations also derived benefit from alpelisib, which will inform clinical decision-making moving forward. See related article by Rugo et al., p. 1056.

Publication types

  • Editorial
  • Research Support, N.I.H., Extramural
  • Comment

MeSH terms

  • Biology
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / pathology
  • Class I Phosphatidylinositol 3-Kinases / genetics
  • Female
  • Humans
  • Mutation
  • Phosphatidylinositol 3-Kinases* / genetics
  • Prospective Studies


  • Alpelisib
  • Phosphatidylinositol 3-Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human