Alpelisib Efficacy without Cherry-PI3King Mutations

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.

Automated summary

The PI3K inhibitor alpelisib is approved for treating metastatic estrogen receptor-positive breast cancers with PIK3CA hotspot mutations. Clinical trials have shown the benefits of alpelisib in treating advanced ER+ breast cancers with PIK3CA hotspot mutations in exons 7, 9, and 20. However, a recent study demonstrates the efficacy of alpelisib in patients with non-hotspot PIK3CA mutations, which has important implications for clinical decision-making.