Published in:
29-06-2022 | Colorectal Cancer | Original Research Article
Prognostic and Predictive Value of PIK3CA Mutations in Metastatic Colorectal Cancer
Published in: Targeted Oncology | Issue 4/2022
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Background
Comprehensive genomic profiling is used to guide the management of metastatic colorectal cancer (mCRC); however, the role of PIK3CA mutations, present in up to 20% of mCRCs, is unclear.
Objective
This study aimed to evaluate the association of PIK3CA mutations with other common mutations in mCRC and determine the prognostic and predictive value of PIK3CA mutations.
Patients and Methods
A retrospective chart review was performed on patients in the Moffitt Clinical Genomic Database with mCRC. A meta-analysis was performed to further evaluate the predictive value of PIK3CA mutations to the response to anti-epidermal growth factor receptor (EGFR) therapy.
Results
Among 639 patients, PIK3CA was positively correlated with KRAS mutation (r = 0.11, p = 0.006) and negatively correlated with TP53 mutation (r = − 0.18, p ≤ 0.001) and ERBB2 amplification (r = − 0.08, p = 0.046). The median overall survival (OS) of patients with PIK3CA-mutant mCRC (n = 49) was 35.5 (95% confidence interval [CI] 18.7–48.1) months vs. 55.3 (95% CI 47.5–65.6) months for PIK3CA wild-type mCRC (n = 286) [p = 0.003]. This OS difference remained significant with exon 9 and exon 20 subset analyses. There was no significant difference in response rate between patients with PIK3CA wild-type (n = 97) versus mutant (n = 9) mCRC who received anti-EGFR therapy (43% vs. 56%, p = 0.61) and no significant difference in median progression-free survival (PFS) of 10.3 versus 7.2 months (p = 0.60). However, our meta-analysis of 12 studies, including ours, using a common effect model identified that PIK3CA mutations are associated with reduced response to anti-EGFR therapy, with a relative risk of 0.56 (95% CI 0.38–0.82).
Conclusion
Our study identified PIK3CA mutations as a poor prognostic factor, and our meta-analysis identified PIK3CA mutations as predictive of decreased response to anti-EGFR therapy in patients with mCRC.