106P - Clinical application of next-generation sequencing in metastatic colorectal cancer (mCRC): Experience from a comprehensive cancer centre

Background

Next-generation sequencing (NGS) is a valuable tool for tailored treatment (ttm) selection in advanced cancer patients (pts). ESMO strongly recommends that clinical research centres perform NGS in mCRC pts to promote cancer research and drug development, provide access to innovation and data collection. The aim of this study is to assess the utility of an expanded genomic profiling programme in a single institution for mCRC pts to allow access to targeted therapies and clinical trials.

Methods

Retrospective analysis of a prospectively registered cohort of mCRC pts with tumour molecular profile assessed within daily clinical practice. OncomineTM Precision Assay (OPA) panel (Thermofisher®) was used as first genomic test for newly diagnosed pts, added to the analysis of mismatch repair (MMR) system status by usual techniques. TruSightTM Oncology 500 (TSO) panel (Illumina®) was used in refractory pts with the aim of searching new ttm options in clinical trials.

Results

A total of 136 samples (108 primary tumour and 28 metastases) from mCRC pts were analysed between March 2022 and March 2023. Median age was 64 (15-83) years old and 47 (34.5%) were women. OPA was used in 111 (81.6%) new pts and TSO in 25 (18.3%) refractory pts. Data were unavailable in 5 pts (3.6%) due to technical issues, but molecular testing could be done by single-gene approach. Median turnaround time (TAT) was 13.4 days (4-43) with OPA and 25 (15-70) with TSO. Most frequent alterations were KRAS mutations in 68 pts (G12C 2.2%, G12V 11.8%, G12D 14.7% and others 21.3%); BRAFV600E was detected in 12 pts (8.8%) and NRAS in 4 (2.9%). MSI-high by NGS had a 100% correlation with other techniques, but 3/9 (33.3%) dMMR tumours were stable by NGS. Eleven out of 25 pts (44%) with an actionable target (BRAFV600E, KRASG12C, MSI-high and TMB high) had access to innovative targeted drugs and/or clinical trial.

Conclusions

NGS testing performed in highly qualified centres is feasible, with an optimal TAT and low frequency of technical failures. Of note, NGS programme allows the access to innovative therapies in almost half of the mCRC pts with an actionable target. Further studies, including cost-effectiveness analysis, need to be performed with larger real-world cohorts.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

J.C. Ruffinelli: Financial Interests, Personal, Invited Speaker: Amgen; Other, Personal, Other, Travel and accommodation: MSD, Merck, Advanced Accelerator Applications.C. Santos Vivas: Financial Interests, Personal, Advisory Board: Sanofi, Amgen, Pierre Fabre; Financial Interests, Personal, Other, Travel and Accommodation: Merck KGaA. All other authors have declared no conflicts of interest.