Abstract 105P
Background
PIK3CA mutations (PIK3CAm) have been described as a mechanism of resistance to anti-EGFR agents in mCRC. However, its prognostic impact and the feasibility of liquid biopsy in its detection remain unknown. We aim to analyze the clinicopathological features and the outcomes according to PIK3CA & RAS/BRAF status in tissue & plasma in mCRC.
Methods
We conducted a retrospective and unicentric study of PIK3CA mutational status in tissue & plasma samples in patients (pts) with mCRC from 2017 to 2024. PIK3CA test was performed by Cobas®PIK3CA Mutation Kit. We used Kaplan-Meier and Cox models to analyze the overall survival (OS) in PIK3CAm vs wild-type (WT), and its prognosis according to RAS/BRAF status.
Results
We analyzed 168 paired samples from 84pts with mCRC (both in tissue & plasma). PIK3CAm were found in 18pts (21.4%), of which 19% (16pts) were detected in tissue and 11.9% (10pts) in plasma. Liver involvement was more frequent in PIK3CAm vs WT (94.4% vs 63.6%; p=0.01); unlike lymph node/peritoneal involvement (5.6% vs 31.8%; p=0.03). The concordance analysis (tissue & plasma) showed a moderate kappa index (0.49). We found PIK3CAm by both methods in 7pts (8.3%) and mismatches in 11pts (13.1%). There was a trend towards worse OS in PIK3CAm vs WT (22.6m vs 28.1m, p=0.81). Plasma PIK3CAm detection did not correlate with OS after adjusting by liver involvement, HR=1.57; p=0.24. Also, we assessed prognosis in pts with PIK3CAm in tissue & discordant plasma results, detecting poorer OS in mutated plasma pts (16.4m vs 42.5m, HR=2.40; p=0.18).PIK3CAm were evenly distributed in RAS/BRAF WT vs mutated tumors (50% vs 51.5%; p=0.92). We found no independent prognostic impact of PIK3CAm in OS after stratifying by RAS/BRAF status; in RAS/BRAF WT pts (41.3m vs 36.2m; p=0.93) and in RAS/BRAFm (22.6m vs 26.4m; p=0.91). Table: 105P
| PIK3CA tissue | ||||
| PIK3CA Plasma | Mutated n (%) | WT n (%) | Total n (%) | |
| Mutated | 7 (43.8) | 2 (2.9) | 9 (10.7) | |
| WT | 9 (56.3) | 66 (97.1) | 75 (89.3) | |
| Total | 16 (100) | 68 (100) | 84 (100) | |
| Positive agreement: 72/16: 43.8% | ||||
| Negative agreement: 66/68: 97.1% | ||||
| Overall agreement: 73/84: 86.9% |
Conclusions
Our results support the potential value of liquid biopsy in the detection of PIK3CAm in mCRC. PIK3CAm did not show prognostic value after adjusting OS by liver involvement and RAS/BRAF status.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
R. Vidal Tocino: Financial Interests, Personal, Invited Speaker: Amgen, Merck, Servier, Bristol-MS, Bayer, MSD; Financial Interests, Personal, Advisory Board: Servier, GSK; Non-Financial Interests, Member: ACLO- Asociación Castellano-leonesa de Oncología, SEOM- Sociedad Española de Oncología Médica; Other, Travel and accommodation: Servier, Roche, MSD. R. Lozano Mejorada: Financial Interests, Personal, Invited Speaker: Janssen, Astellas, Roche, Bayer, Ipsen, AstraZeneca; Financial Interests, Personal, Advisory Board: Janssen, Merck/Pfizer, Orion Pharma, Advanced Accelerator Applications (Novartis); Financial Interests, Personal, Other, Travel/accommodation: MSD, Sanofi; Financial Interests, Personal, Other, Travel/accommodation: BMS; Non-Financial Interests, Member: Sociedad Española de Oncología Médica. All other authors have declared no conflicts of interest.