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
5368 - Durvalumab and Paclitaxel Combination for treatment of metastatic triple negative breast cancer is safe with very promising efficacy
Presenter: Hazem Ghebeh
Session: Poster Display session 3
Resources:
Abstract
1520 - A prospective cohort study on the pharmacokinetics of nivolumab in metastatic non-small cell lung cancer, melanoma, and renal cell cancer patients
Presenter: Daan Hurkmans
Session: Poster Display session 3
Resources:
Abstract
1603 - Safety and clinical activity of subcutaneously (SC) administered anti-PD-1 antibody PF-06801591 in phase I dose-expansion cohorts of locally advanced or metastatic non-small-cell lung cancer (NSCLC) and urothelial carcinoma (UC)
Presenter: Byoung Cho
Session: Poster Display session 3
Resources:
Abstract
3922 - Development of the Functional Assessment of Cancer Therapy-Immune Checkpoint Modulator (FACT-ICM): A scale to measure quality of life in cancer patients treated with ICMs
Presenter: Aaron Hansen
Session: Poster Display session 3
Resources:
Abstract
2408 - Immune checkpoint inhibitors (ICIs) as “chemotherapy (Ctx) sensitization” strategy in advanced solid tumors
Presenter: Francisco Javier Ros Montana
Session: Poster Display session 3
Resources:
Abstract
3612 - Validation of progression-free survival (PFS) as surrogate endpoint in randomised trials of immune checkpoint inhibitors in advanced solid cancers
Presenter: Peey Sei Kok
Session: Poster Display session 3
Resources:
Abstract
3827 - Pharmacokinetic (PK) analysis of weight-based and fixed dose cemiplimab in patients (pts) with advanced malignancies
Presenter: Michael Migden
Session: Poster Display session 3
Resources:
Abstract
2120 - A burst of highly differentiated CD4 TL identifies a subset of fast progressors, and correlates with hyperprogressive disease in NSCLC patients treated with ICI
Presenter: Hugo Arasanz
Session: Poster Display session 3
Resources:
Abstract
4254 - Nivolumab treatment in advanced non-small cell lung cancer (aNSCLC): a French nationwide retrospective cohort (UNIVOC Study)
Presenter: Christos Chouaid
Session: Poster Display session 3
Resources:
Abstract
1084 - Dissociated responses in patients with metastatic solid tumors treated with immunotherapy
Presenter: Pauline Vaflard
Session: Poster Display session 3
Resources:
Abstract