247P Efficacy of therapy directed against PI3K and cyclin inhibitors based on the location of PI3K mutations

Activation of the phosphatidylinositol-3-kinase (PI3K) pathway is responsible activating phosphorylation cascade that regulates cell survival and metabolism. Mutations in this may occur 28-46% HR+/HER2- advanced breast cancers. It known presence mutation confers a worse prognosis. We set out to analyze if PI3K mutations different exons confer resistance treatments directed against target cyclin inhibitors (inh-CDK4/6). have analyzed 96 patients with cancer subsidiaries treatment PI3K-targeted therapy hospital Jaén from February/20 January/23. To detect PIK3CA we used cobas ® diagnostic kit detects: 1 (R88Q), 4, 7 (C420R), 9 (E542K, E545K/A/D/G, Q546E/R) 20 (H1047R/Y/L). obtained 26% (5% exon 1, 40% 9, 55% 20). All women mean age at diagnosis 48 years 56 metastases, located bone 65%, lung 35%, liver 23% CNS 4% been treated inh-CDK4/6. The median progression-free (mSLP) 17 months (1-60). In mutation, mSLP 25 months, 13 (2-43) 20, 19 (1-60) 60% progressed inh-CDK4/6 as next alpelisib. 58% corresponds 2 line metastatic disease. 5 (1-22) follow-up 14 (1-34) 69% events. (1-13) (2-22). Treatment was associated an antiestrogen (77%) or aromatase inhibitor 3 (2-10). 53% suffered grade adverse effects (G3 AE): hyperglycemia (80% 16% 20), diarrhea (20% 9) skin rash (16% 14% discontinued due toxicity. PFS alpelisib lower than reported SOLAR1 study similar Bylieve study, whose population most our sample. Exon carriers are those who obtain higher PFS, well receive it antiestrogen. rate G3 AE With respect inh-CDK4/6, literature, obtaining PFS.