Clinical Impact of High Throughput Sequencing on Liquid Biopsy in Advanced Solid Cancer

Abstract

Background: Cancer therapies targeting actionable molecular alterations (AMA) have developed, but the clinical routine impact of high-throughput molecular profiling remains unclear. We present a monocentric experience of molecular profiling based on liquid biopsy in patients with cancer. Methods: Patients included had solid cancer and underwent cfDNA genomic profiling with FoudationOne Liquid CDx (F1LCDx) test, analyzing 324 genes. Primary endpoint was to describe patients with an AMA for whom clinical decisions were impacted by F1LCDx test results. Results: 191 patients were included, mostly with lung cancer (46%). An AMA was found in 52%. The most common molecular alterations were: TP53 (52%), KRAS (14%) and DNMT3 (11%). The most common AMA were: CHEK2 (10%), PIK3CA (9%), ATM (7%). There was no difference in progression-free survival (2.66 months vs. 3.81 months, p = 0.17), overall survival (5.3 months vs. 7.1 months, p = 0.64), or PFS2/PFS1 ratio ≥ 1.3 (20% vs. 24%, p = 0.72) between patients receiving a molecularly matched therapy (MMT) or a non-MMT, respectively. Patients with a MMT had an overall response rate of 19% and a disease control of 32%. Conclusions: Routine cfDNA molecular profiling is feasible and can lead to the access of targeted therapies. However, no notable benefit in patient’s outcomes was shown in this unselected pan-cancer study.

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 patients in the present cohort had on average received extensive pre-treatment with at least two lines of treatment (20), except in the case of brain tumors which were included earlier. This is consistent with the report by Gouton et al, in which the median prior lines of systemic therapy was 3 (range, 0-10) (21). In this study, administration of genotype-directed therapy had no impact on the patient's OS (13 months vs. 14 months, p = 0.95, HR = 1.04).…”

“…The percentage of patients with 4-5 alterations in at least one gene belonging to a KEGG pathway are indicated in a yellow-to-red gradient (yellow = <30%; orange = ≥30% and <50%; and red = ≥ 50%). (21). A recent French study that compared the results of FMI analysis between matched FFPE and liquid samples showed that the number of actionable alterations was identical in 42% of cases; in the remaining cases, the number of actionable alterations detected was higher in tissue (35%) than in ctDNA (23%) samples (9).…”

Blood-Derived Liquid Biopsies Using Foundation One® Liquid CDx for Children and Adolescents with High-Risk Malignancies: A Monocentric Experience

“…In adults, recently, analysis of cell-free DNA extracted from the blood is a recognized tool in non-small-cell lung cancer international practice guidelines [ 26 ], mostly for disease monitoring, and provides several advantages compared to analysis performed via tissue biopsy [ 27 ]. A recent study by Gouton et al was the first to evaluate the feasibility and clinical impact of liquid biopsy for cell-free DNA-based NGS analysis in pan-cancer patients, also using F1LCDx [ 28 ].…”

An Overview of Comprehensive Genomic Profiling Technologies to Inform Cancer Care

“…62 One study examined the use of a liquid biopsy-based CGP at a single centre for a variety of cancers, including lung, breast, pancreatic, and colorectal cancers. 63 The authors noted that participants in the study were heavily pre-treated (with a median of 3 prior lines of systemic therapy), which made it difficult to draw meaningful conclusions about comparative benefits. However, they stated that it would be preferrable to provide precision-based therapies in early-stage disease.…”

“…However, they stated that it would be preferrable to provide precision-based therapies in early-stage disease. 63 Although further research is needed, findings from these emerging studies suggest that liquid-based CGP clinical performance is not inferior to other tests used in routine care.…”