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.
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.
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).
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.
NCT02840604.
François Ghiringhelli.
Centre Georges-François Leclerc.
All authors have declared no conflicts of interest.