1555P - Cell-free DNA analysis in patients with metastatic gastroesophageal adenocarcinoma: Preliminary results of the REGIRI - PRODIGE 58 ancillary study

Background

Cell-free DNA (cfDNA) analysis has shown promising results for the management of patients with cancer, but few data exist in patients with metastatic gastro-esophageal adenocarcinomas (mGEA). In this study, we analyzed cfDNA extracted from blood of patients included in the REGIRI - PRODIGE 58 trial (Regorafenib + irinotecan as 2^nd line in patients with mGEA).

Methods

239 samples from 34 patients with mGEA included in the Regiri arm were available for analysis. Plasma samples were taken before treatment’s initiation, then at days 1, 2, 8 and 15 of Cycle 1 and days 1, 8 and 15 of Cycle 2. cfDNA was extracted from plasma, concentrations and fragments sizes determined by fragment analysis. First and last time points were selected to estimate concentration’s evolution for each patient.

Results

A cfDNA threshold concentration (tc) of 0.55 ng/μL was settled as the best threshold at baseline to separate patients into 2 groups “low” and “high” corresponding to concentrations lower or greater than tc respectively. Among the 34 patients analyzed, 1 patient was excluded because of genomic DNA contamination in plasma at baseline. 16 patients (48.48%) were in the “low” group and 17 (51.52%) in the “high” group. For cfDNA concentration at baseline and PFS, a trend non-statistically significant difference (HR=0.53; CI95[0.2595;1.085]; p=0.0564) was found: Low cfDNA concentration at baseline was associated with a better PFS (2.6 vs 1.7 months). 4 distinct subgroups emerged: Patients with low concentration at baseline that remains low (low-low), low at baseline with an increase during follow-up (low-high), high at baseline with a decrease during follow-up (high-low) and high at baseline that remains high (high-high). A statistically significant difference was found for PFS (4.55 vs 2.11 months) between the low-low and high-high subgroups respectively (HR=0.4139; CI95[0.1652;1.037]; p=0.022).

Conclusions

Our findings suggest that cfDNA concentration at baseline and cfDNA clearance might have an interest to predict PFS in patients with mGEA. Further investigations are ongoing to decipher if genomic signatures can be predictive of PFS in patients with mGEA.

Clinical trial identification

NCT03722108.

Editorial acknowledgement

Legal entity responsible for the study

UNICANCER.

Funding

Has not received any funding.

Disclosure

A. Harlé: Financial Interests, Personal and Institutional, Expert Testimony, Hospitality, travels and honoraria: Amgen, Archer Invitae, AstraZeneca, Biocartis, BMS, GSK, Merck, Novartis, Pfizer, Roche, Sanofi, Sophia Genetics, Tesaro; Financial Interests, Personal, Expert Testimony, Honoraria: Apelo Consulting, B3TSI, Diaceutics, HederaDX, Icomed, Janssen, Pierre Fabre, QualWorld; Financial Interests, Personal and Institutional, Expert Testimony, Honoraria: BioRad, Decibio; Non-Financial Interests, Institutional, Expert Testimony, Hospitality: Boehringer Ingelheim; Non-Financial Interests, Personal and Institutional, Expert Testimony, Hospitality and travels: Illumina; Financial Interests, Personal and Institutional, Expert Testimony, Hospitality and honoraria: MSD; Financial Interests, Personal and Institutional, Expert Testimony, Hospitality and travels: Sysmex Inostics. L. Evesque: Financial Interests, Personal, Advisory Board: Servier, Amgen, MSD, Merck. A. Turpin: Financial Interests, Personal, Expert Testimony: Merck, Viatris, Incyte Biosciences; Financial Interests, Personal, Advisory Board: Servier, AstraZeneca, MSD, BMS. D. Tougeron: Financial Interests, Personal, Advisory Board: AstraZeneca, Sanofi, Amgen, MSD, Roche, Servier, Pierre Fabre, BMS, Bayer; Non-Financial Interests, Member of Board of Directors: Federation francophone de cancerologie digestive. D. Botsen: Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Amgen, Servier, Sanofi, Pierre Fabre Merck, Accord Healthcare. M. Muller: Financial Interests, Institutional, Invited Speaker: Servier. C. de la Fouchardiere: Financial Interests, Personal, Advisory Board: Merck, Roche, Lilly, Bayer, Amgen, MSD, Servier, Pierre Fabre Oncologie, Bristol Myers Squibb, Incyte, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Ipsen, Eisai, Servier, MSD, Daiichi Sankyo; Financial Interests, Institutional, Coordinating PI: Pierre Fabre Oncologie, Servier; Non-Financial Interests, Principal Investigator: Amgen, Daiichi Sankyo, MSD. O. Dubreuil: Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Invited Speaker: Sanofi, Pierre Fabre, Servier, MSD, AstraZeneca. O. Bouche: Financial Interests, Personal, Advisory Board: Amgen, Merck, Apmonia Therapeutics, Deciphera; Financial Interests, Personal, Invited Speaker: Servier, Pierre Fabre, Bayer. F. Khemissa Akouz: Financial Interests, Personal, Invited Speaker: Servier. J.L. Merlin: Financial Interests, Personal, Expert Testimony: Amgen, BMS, MSD, Pfizer, Pierre Fabre, Servier; Financial Interests, Personal and Institutional, Expert Testimony: AstraZeneca, GSK, Merck, Novartis; Non-Financial Interests, Institutional, Expert Testimony: Biocartis; Non-Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Expert Testimony: Sophia Genetics. E. Samalin-Scalzi: Financial Interests, Personal, Advisory Board: Pierre Fabre Onoclogy, Servier France, Astellas Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Advisory Board: MSD; Financial Interests, Institutional, Coordinating PI: Bayer; Non-Financial Interests, Member of Board of Directors: Unicancer GI PRODIGE. All other authors have declared no conflicts of interest.