Abstract 1239: Prognostic and predictive value of PIK3CA mutations in metastatic CRC (mCRC)

Background: Molecular aberrations including MSI, RAS, RAF, and HER2 have been used to guide the management of mCRC. However, the role of PIK3CA mutations is unclear in mCRC. In this study, we aimed to determine the prognostic value of PIK3CA mutations and their predictive value of response to anti-EGFR therapy in mCRC patients (pts). Methods: Pts with mCRC and clinical next generation sequencing were identified from the Clinical Genomics Action Committee database at Moffitt Cancer Center. Clinical and molecular aberration data were retrospectively collected. Progression-free survival (PFS) was the time from treatment initiation to clinical or radiographic disease progression. Overall survival (OS) was the time from diagnosis of metastatic disease to death. Kaplan Meier method and log-rank test were used for survival analysis. A parametric exponential model was implemented for PIK3CA exon analysis to account for small sample size. Pearson correlation coefficient was determined for correlation between PIK3CA and co-mutations. An additional meta-analysis was performed including prior studies of pts with KRAS wild-type (wt) PIK3CA mutant (mut) mCRC receiving anti-EGFR therapy using random effects model. Results: Among 639 pts with mCRC, PIK3CA mutation was positively correlated with KRAS mutation (r=0.11, p=0.006) and negatively correlated with TP53 mutation (r=-0.18, p= Conclusion: PIK3CA mutation has positive correlation with KRAS mutation and negative correlation with TP53 mutation in mCRC. PIK3CA mutation confers a worse prognosis but is not predictive for response to anti-EGFR therapy in pts with KRAS wt mCRC. The latter finding was confirmed in an updated meta-analysis of 13 studies including ours. Citation Format: Elaine Tan, Wenyi Fan, Michael Schell, Ibrahim Sahin, Jason Fleming, Todd Knepper, Hao Xie. Prognostic and predictive value of PIK3CA mutations in metastatic CRC (mCRC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1239.