4CPS-004 Real-world outcomes of alpelisib: implications of PIK3CA variants

<h3>Background and Importance</h3> Among the multiple PIK3CA gene variants, only 11 of them have been represented in randomised controlled trials (RCT) of alpelisib, mainly in pivotal trials BYLieve and SOLAR-1. <h3>Aim and Objectives</h3> To evaluate alpelisib results in real-world setting and assess whether there are different findings in population with PIK3CA mutations other than the ones included in above-mentioned RCT. <h3>Material and Methods</h3> Ambispective observational study of patients with locally advanced or metastatic PIK3CA-mutated breast cancer treated with alpelisib plus fulvestrant between November 2019 and March 2024, previously treated with CDK4/6 inhibitors and an aromatase inhibitor, with ECOG performance status of 0 or 1. Patients were classified in two groups: group 1 did NOT have variants included in RCT; group 2 did. Effectiveness was evaluated through progression-free survival (PFS) and overall survival (OS) medians using the Kaplan-Meier method. Then, log-rank tests were performed to verify statistically significant differences between groups. R Commander software was used for statistical analysis. <h3>Results</h3> 31 patients, all women (median age 61.76 [range 34.17–76.83]), received alpelisib therapy, although 3 were excluded from analysis due to off-label use. Median treatment duration: 6.71 months (range: 1.61–39.93). Group 1: 5 patients; Group 2: 21 patients; 2 patients were excluded from subgroup analysis (as PIK3CA variant has not been reported). <h3>Total population</h3> PFS was 6.89 months (95% confidence interval [CI], 4.49–12.33). OS was 20, 59 months (95% CI: 16.92-Not reached (NR)). As compared to phase III RCT SOLAR-1 results, our study showed lower PFS (6.89 vs 11.0 months), but similar to other real-world cohorts. <h3>Subgroup analysis</h3> Group 1. PFS: 13.90 months (95% CI = 6.89, NR). OS 20, 59 months (CI 95% = 15.61, NR). Group 2. PFS: 5.61 months (95% CI = 3.41, 12, 33). OS: NR (CI 95% = 11.21, NR). There were no statistically significant differences in PFS or OS between groups (p = 0.09 and p = 0.3, respectively). Nonetheless, results suggest a trend in favour of group 1 outcomes. <h3>Conclusion and Relevance</h3> Our results show a modest benefit observed with alpelisib in real-world clinical practice when used as second-line therapy. Finally, the clinical utility of PIK3CA mutations requires further research that to detect potential benefits from mutation guided treatment algorithms to optimise and ease clinical decisions, improving outcomes. <h3>References and/or Acknowledgements</h3> <h3>Conflict of Interest</h3> No conflict of interest