Abstract 1209
Background
Genomically-guided clinical trials began to evaluate the efficacy of molecularly-targeted therapies across different tumor types sharing genetic mutations, but trial organisation remains complex. Here we address the feasibility and utility of routine somatic and constitutional exome analysis in a prospective cohort of metastatic cancer patients.
Methods
Exoma trial is a multicenter, prospective clinical trial to test whether exome analysis is feasible and improves access to targeted therapies in routine care. Eligible patients presented a metastatic cancer progressing after at least one line of systemic therapy. Constitutional genetics testing required geneticist consultation. Somatic and constitutive exome analysis was restricted to 342 genes adapted from Foundation Medicine gene list. Variants were classified using Tier models and molecular tumor board made therapeutic recommendations based on ESMO guidelines. Primary endpoint was PFS2/PFS1 ratio.
Results
Between May 2016 and October 2018, 506 patients were included. The main tumor type was breast cancer, followed by colorectal and pancreatic cancer. Median time required for tumor sample reception was 8 days. Median time from sample reception to results was 52 days. Somatic analysis was performed for 456 patients (90.1%). Both somatic and constitutional analyses were performed for 386 patients (76.3%). The most frequently altered gene was TP53 (38.6%), followed by KRAS (18%) and PIK3CA (13.8%). In total, 342 patients (67.5%) received a therapeutic proposal, including change in chemotherapy or addition of an antiangiogenic drug. 79 patients (15.6%) were treated with NGS matched therapy (PIK3/mTOR inhibitors (27.8%), PARP inhibitors (24%), tyrosine kinase inhibitors (21.5%) or immunotherapy (11.4%)). Data for both PFS2 and PFS1 were available for 148 patients (29.2%). PFS2/PFS1 ratio was > 1,3 for 23,5% of patients treated with the NGS matched therapy (n = 51) and 23,7% of patients treated with standard therapy (n = 97).
Conclusions
Study shows that exome analysis is feasible in cancer routine care, improves detection of genetic predispositions and enhances access to target therapies. However, no differences were observed between PFS ratios of patients treated with matched therapy versus standard.
Clinical trial identification
NCT02840604.
Editorial acknowledgement
Legal entity responsible for the study
François Ghiringhelli.
Funding
Centre Georges-François Leclerc.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4097 - Targeting NRG1-fusions in multiple tumour types: Afatinib as a novel potential treatment option
Presenter: Stephen V Liu
Session: Poster Display session 3
Resources:
Abstract
1129 - Aspirin and Ticagrelor for the prevention of tumour cell induced platelet aggregation
Presenter: Meera Chauhan
Session: Poster Display session 3
Resources:
Abstract
4514 - Pharmacokinetic/ pharmacodynamic (PK/PD) exposure-response characterization of GSK3359609 (GSK609) from INDUCE-1, a phase I open-label study
Presenter: Michele Maio
Session: Poster Display session 3
Resources:
Abstract
5169 - In vitro functional interrogation of viable Circulating Tumor Associated Cells (C-TACs) for evaluating Platin resistance.
Presenter: Stefan Schuster
Session: Poster Display session 3
Resources:
Abstract
5827 - Targeting ARG2 as a novel therapeutic approach for cancer
Presenter: Marcin Grzybowski
Session: Poster Display session 3
Resources:
Abstract
3129 - MPS1 and PLK1 as new therapy targets in TP53 mutated solid tumors
Presenter: Balazs Gyorffy
Session: Poster Display session 3
Resources:
Abstract
2129 - The Tumor Static Exposure (TSE) concept & utility: application to combination treatment of radiation and radiosensitizing agent in tumor xenograft experiments
Presenter: Samer El Bawab
Session: Poster Display session 3
Resources:
Abstract
1814 - General Methodology to Optimize Tumor Treating Fields Delivery Utilizing Numerical Simulations
Presenter: Noa Urman
Session: Poster Display session 3
Resources:
Abstract
3010 - The Australian Exceptional Responders Program: a National collaboration
Presenter: Megan Barnet
Session: Poster Display session 3
Resources:
Abstract
4489 - A Window of Opportunity Trial of Atorvastatin Targeting p53 Mutant Malignancies
Presenter: Joaquina Baranda
Session: Poster Display session 3
Resources:
Abstract