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Genomic Determinants of Response to Alpelisib Plus Fulvestrant in the SOLAR-1 Trial - PubMed

5 hours ago
  • #Breast Cancer
  • #Alpelisib
  • #Genomic Determinants
  • Alpelisib combined with fulvestrant significantly improves median progression-free survival (11.01 months) compared to placebo plus fulvestrant (5.55 months) in PIK3CA-altered HR+/HER2- advanced breast cancer.
  • Patients with low tumor mutational burden or FGFR1/FGFR2 alterations derive greater PFS benefit from alpelisib plus fulvestrant, while those with MYC or RAD21 alterations see limited benefit.
  • Cox and machine learning models identified poorer ECOG performance status, prior CDK4/6i treatment, and PTEN or TP53 alterations as negative prognostic factors for PFS in PIK3CA-altered patients.
  • Genomic profiles differ between PIK3CA-altered and PIK3CA-wild type tumors, with alpelisib showing efficacy across various concomitant alterations, including those linked to therapy resistance.
  • The study supports alpelisib plus fulvestrant as beneficial for PIK3CA-altered advanced breast cancer, with genomic factors influencing treatment response identified through NGS and machine learning.