A. Galvano (Palermo, Italy)
AOU Policlinico "Paolo Giaccone"Author Of 1 Presentation
- L. Castellana (Palermo, Italy)
- V. Gristina (Palermo, Italy)
- A. Galvano (Palermo, Italy)
- M. La Mantia (Palermo, Italy)
- L. Insalaco (Palermo, Italy)
- N. Barraco (Palermo, Italy)
- S. Cutaia (Palermo, Italy)
- F. Iacono (Palermo, Italy)
- G. Santanelli (Palermo, Italy)
- A. Cucinella (Palermo, Italy)
- G. Madonia (Palermo, Italy)
- M. Ricciardi (Palermo, Italy)
- M. Lisanti (Palermo, Italy)
- V. Calò (Palermo, Italy)
- M. Castiglia (Palermo, Italy)
- A. Perez (Palermo, Italy)
- S. Cusenza (Palermo, Italy)
- S. Rizzo (Palermo, Italy)
- A. Russo (Palermo, Italy)
- V. Bazan (Palermo, Italy)
20P - Is evaluation of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutational status on circulating tumor DNA (ctDNA) by liquid biopsy ready for prime-time? A systematic review and an individual patient meta-analysis
Abstract
Background
PIK3CA represents one of the most mutated genes, both in hormone receptor-positive BC and HER2-positive ones. Several clinical trials demonstrated that the detection of PIK3CA mutations in ctDNA could represent a predictive biomarker of PI3K-inhibitor treatment response. BELLE-2, BELLE-3, and SOLAR-1 trials prospectively showed a significant progression-free survival benefit in ctDNA PIK3CA-mutant patients, suggesting PIK3CA mutation detection in ctDNA could represent a PI3K-Is predictive biomarker. Still, it would seem that liquid biopsy could be potentially more reliable than a tissue biopsy, as emerged from the BELLE-2 study. Yet, the diagnostic accuracy of liquid biopsy in detecting mutations on PIK3CA in BC is still being evaluated.
Methods
Our purpose was to provide a comparative analysis of diagnostic accuracy between tissue and liquid biopsies. Moreover, we deeply investigated if different diagnostic molecular techniques could influence the accuracy of liquid biopsy in detecting PIK3CA mutation. Variables which could potentially affect the results (technique, tumor burden, time elapsed between tissue and blood samples collection) were considered. The pooled analysis was carried out on 25 works for a total of 1966 patients, for which matched tumor tissue and plasma specimens have been collected.
Results
The results proved a better performance of NGS-based technologies in terms of sensitivity and specificity compared to ddPCR/BEAMing and Real Time-Polymerase Chain Reaction (RT-PCR). In particular, we reported AUC values for NGS-based assays of 0,98 (ddPCR/BEAMing 0,92; PCR 0,77), resulting in absence of significant heterogeneity for the pooled specificity (I2 = 0 %, Cochran’s Q test p-value = 0.52).
Conclusions
We would suggest the use of NGS rather than conventional RT-PCR to screen for the presence of a PIK3CA mutation in BC patients. Finally, given the not well-established applications of ctDNA analysis in the clinical management of BC, this meta-analysis could add intriguing insights supporting the introduction of liquid biopsy in clinical practice as a routine procedure.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
A. Russo: Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Ambrosetti; Advisory/Consultancy: Kyowa Kirin; Speaker Bureau/Expert testimony: Roche Diagnostics. All other authors have declared no conflicts of interest.