Abstract 101P
Background
PIK3CA mutation status is an established predictive biomarker in BC; alpelisib is now approved for pts with luminal PIK3CA-mutated advanced BC. Several studies reported heterogeneous diagnostic accuracy degrees in detecting PIK3CA mutations in ctDNA compared to the gold standard assessment on TT. We conducted a meta-analysis to estimate the overall diagnostic accuracy of PIK3CA mutations evaluated using ctDNA as compared to TT.
Methods
A literature systematic review retrieving articles from PubMed/MEDLINE, Cochrane, EMBASE databases and abstracts from ASCO, ESMO, ESMO Breast and SABCS meetings, up to February 2020 was conducted. Studies providing PIK3CA mutation status both on TT and matched plasma samples in BC pts were eligible. True positive, false negative, true negative, and false positive data were extracted. Pooled sensitivity (SE), specificity (SP), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were calculated. Exploratory subgroup analyses by BC stage and subtype, and timing and methods of PIK3CA mutation detection were performed.
Results
31 studies including a total of 34 cohorts and 1,952 pts were eligible. The pooled SE and SP of detecting PIK3CA mutations on ctDNA as compared to TT were 0.74 (95% CI 0.68-0.82) and 0.95 (95% CI 0.92-0.98), respectively. The pooled PLR and NLR were 6.2 (95% CI 4.2-9.2) and 0.38 (95% CI 0.30-0.49), respectively. The DOR was 23.2 (95% CI 14.5-37.1) and AUC was 0.81 (95% CI 0.77-0.85). Significant heterogeneity among the included studies was observed (SE: I 2 67.6%, p<0.001; SP: I 2 55.8%, p<0.001). Absence of heterogeneity accompanied by higher overall diagnostic accuracy was found for pts whose PIK3CA mutations were assessed on ctDNA drawn within 60 days from TT biopsy, or through real-time PCR or NGS methods. No publication bias was found (p=0.318).
Conclusions
The high overall diagnostic accuracy of PIK3CA mutation detection on ctDNA observed in this meta-analysis supports the use of this method in clinical practice. ctDNA is simple and easily performed and can be assessed at multiple moments of the metastatic disease course.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Claudia De Angelis.
Funding
Has not received any funding.
Disclosure
R. Caparica: Speaker Bureau/Expert testimony, speaker honoraria: Boehringer-Ingelheim; Speaker Bureau/Expert testimony, speaker honoraria: AstraZeneca; Speaker Bureau/Expert testimony, speaker honoraria: Janssen; Travel/Accommodation/Expenses: Astrazeneca; Travel/Accommodation/Expenses: Pfizer. A. Falcone: Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Bayer; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Bristol; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Lilly; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Merck; Honoraria (self), Advisory/Consultancy: Pierre-Fabre; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (self): Roche; Honoraria (self), Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Servier; Honoraria (institution), Research grant/Funding (institution): AstraZeneca; Honoraria (institution), Research grant/Funding (institution): MSD; Honoraria (institution), Research grant/Funding (institution): Novartis; Honoraria (institution), Research grant/Funding (institution): Sanofi; Leadership role: Fondazione G.O.N.O.; Leadership role: Fondazione ARCO. A. Prat: Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Amgen; Speaker Bureau/Expert testimony: BMS; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Daiichi Sankyo; Advisory/Consultancy: Puma; Advisory/Consultancy: Oncolytics Biotech; Advisory/Consultancy: MSD; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Speaker Bureau/Expert testimony, Research grant/Funding (institution): Nanostring technologies; Research grant/Funding (institution): Boehringer; Research grant/Funding (institution): Roche Pharma; Research grant/Funding (institution): Sysmex Europa GmbH; Research grant/Funding (institution): Medica Scientia inno. Research, SL; Research grant/Funding (institution): Celgene, SLU; Research grant/Funding (institution): Astellas Pharma; Research grant/Funding (institution): Novartis Farma; Leadership role, member executive board: Breast International Group (BIG); Leadership role, member of the board: Solti's Foundation; Leadership role, patronage committee: Actitud frente al cancer Foundation; Leadership role, member executive board: Solti. E. de Azambuja: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche/GNE; Honoraria (self), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: SeaGen; Research grant/Funding (institution), Travel/Accommodation/Expenses: GSK/Novartis; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Servier. M. Lambertini: Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Speaker Bureau/Expert testimony: Lilly; Speaker Bureau/Expert testimony: Takeda; Speaker Bureau/Expert testimony: Theramex. All other authors have declared no conflicts of interest.