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Prognostic and Predictive Value of PIK3CA Mutations in Metastatic Colorectal Cancer

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Abstract

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.

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Authors and Affiliations

  1. Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, USA

    Elaine S. Tan, Ibrahim H. Sahin, Jason B. Fleming & Hao Xie

  2. Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, FL, USA

    Wenyi Fan & Michael J. Schell

  3. Department of Individualized Cancer Management, Moffitt Cancer Center, Tampa, FL, USA

    Todd C. Knepper

Authors
  1. Elaine S. Tan
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  2. Wenyi Fan
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  3. Todd C. Knepper
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  4. Michael J. Schell
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  5. Ibrahim H. Sahin
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  6. Jason B. Fleming
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  7. Hao Xie
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Corresponding author

Correspondence to Hao Xie.

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Funding

No external funding was used in the preparation of this manuscript.

Conflict of interest

Elaine S. Tan, Wenyi Fan, Todd C. Knepper, Michael J. Schell, Ibrahim H. Sahin, Jason B. Fleming, and Hao Xie declare they have no conflicts of interest that might be relevant to the contents of this manuscript.

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki.

Consent to participate

Approval was granted by the Institutional Review Board of Moffitt Cancer Center.

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Not applicable.

Availability of data and material

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code availability

Not applicable.

Author contributions

Conceptualization: ET, TK, HX. Methodology: ET, WF, MS, HX. Formal analysis and investigation: ET, WF, MS, HX. Writing—original draft preparation: ET. Writing—review and editing: TK, MS, IS, JF, HX.

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Tan, E.S., Fan, W., Knepper, T.C. et al. Prognostic and Predictive Value of PIK3CA Mutations in Metastatic Colorectal Cancer. Targ Oncol 17, 483–492 (2022). https://doi.org/10.1007/s11523-022-00898-7

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  • DOI: https://doi.org/10.1007/s11523-022-00898-7