Impact of Next Generation Sequencing on Clinical Practice in Oncology in France: Better Genetic Profiles for Patients Improve Access to Experimental Treatments

Abstract

Objectives: We evaluated how next generation sequencing (NGS) can modify care pathways in an observational impact study in France.Methods: All patients with lung cancer, colorectal cancer, or melanoma who had NGS analyses of somatic genomic alterations done in 1 of 7 biomolecular platforms certified by the French National Cancer Institute (INCa) between 2013 and 2016 were eligible. We compared patients' pathways before and after their NGS results. Endpoints consisted of the turnaround time in obtaining results, the number of patients with at least 1 genomic alteration identified, the number of actionable alterations, the impact of the genomic multidisciplinary tumor board on care pathways, the number of changes in the treatment plan, and the survival outcome up to 1 year after NGS analyses.Results: 1213 patients with a request for NGS analysis were included. NGS was performed for 1155 patients, identified at least 1 genomic alteration for 867 (75%), and provided an actionable alteration for 614 (53%). Turnaround time between analyses and results was on average 8 days (Min: 0; Max: 95) for all cancer types. Before NGS analysis, 33 of 614 patients (5%) were prescribed a targeted therapy compared with 54 of 614 patients (8%) after NGS analysis. Proposition of inclusion in clinical trials with experimental treatments increased from 5% (n = 31 of 614) before to 28% (n = 178 of 614) after NGS analysis. Patients who benefited from a genotype matched treatment after NGS analysis tended to have a better survival outcome at 1 year than patients with nonmatched treatment: 258 days (6107) compared with 234 days (6106), (P = .41).Conclusions: NGS analyses resulted in a change in patients' care pathways for 20% of patients (n = 232 of 1155).

Clinical management of molecular alterations identified by high throughput sequencing in patients with advanced solid tumors in treatment failure: Real-world data from a French hospital

“…The OS results for the patients in the present study should be interpreted with caution because the study was not randomized. However, other studies designed to include patients in clinical trials also showed no increase in OS with matched treatment (8,21,35). For example, Gouton et al showed that in patients treated according to F1LCDx test results, there was no difference in the clinical outcome between those receiving molecularly matched treatment and those receiving nonmolecularly matched treatments (16).…”

“…Although this strategy does not increase survival, the NGS results increase the rate of inclusion in clinical trials of experimental treatments (8,35). For example, Coquerelle et al showed an increase in clinical trial participation from 5% before NGS to 28% after NGS analysis (35).…”

“…Although this strategy does not increase survival, the NGS results increase the rate of inclusion in clinical trials of experimental treatments (8,35). For example, Coquerelle et al showed an increase in clinical trial participation from 5% before NGS to 28% after NGS analysis (35). In any case, these inclusions allow the accumulation of data on the impact of molecular alterations in the response to therapies, the understanding of molecular oncogenic mechanisms and the validation or not of new biomarkers.…”

Brazilian Expert Consensus for NTRK Gene Fusion Testing in Solid Tumors

“…An oncogenic fusion is defined by harboring an in-frame and intact kinase domain 7 In some cases, it may be challenging to properly understand and classify a novel fusion even with RNA sequencing data 17 Optimal turnaround time up to 2 wk 49,50 Turnaround time is highly variable due to pre-analytical factors, sample transportation, and logistics 49,50 frequent in these cancers, such as ETV6::NTRK3, and should be employed if NGS is not accessible or financially viable. However, RNA based NGS panels should be the preferred choice whenever possible.…”

CRAC (Clinical Relevance of Alterations in Cancer): a Knowledge Base for the Selection of Molecularly Matched Therapy for Solid Tumors

“…With the growing use of molecular profiling, the approach to drug treatment of various types of tumors is actively changing [1]. The results of NGS-based genomic testing showed that the use of molecularly matched therapy significantly improves the overall survival of patients with various solid tumors [2][3][4]. Considering the lengthy process of drug approval by regulators for certain indications and their introduction into routine clinical practice, targeted drugs become available in different countries through the active initiation of expanded access (commonly referred to as compassionate use) to therapy programs [5,6].…”