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.
Highlights
Oncogenesis is a complex process due to the accumulation of molecular alterations (MA) involved in the regulation of hallmarks of cancers [1]
We aimed to evaluate the feasibility and clinical utility of highthroughput molecular profiling based on a liquid biopsy in patients with advanced solid cancers, by assessing the proportion of patients treated with an molecularly matched therapy (MMT) and their outcomes
The secondary endpoints were to assess the proportion of patients with solid cancer who presented molecular alterations and actionable molecular alterations (AMA), PFS2 (defined as the progression-free survival on the first therapy after molecular profiling, response rates on treatment 2, overall survival (OS), PFS2/PFS1 ratio (PFS1 being the progression-free survival for the last therapy prior to molecular profiling)
Summary
Oncogenesis is a complex process due to the accumulation of molecular alterations (MA) involved in the regulation of hallmarks of cancers [1]. Current techniques provide an overview of the genomic complexity of primary tumors within a timeframe in accordance with routine practice and at an affordable cost Such advances in sequencing technologies have permitted the identification of genomic alterations that can act as predictive biomarkers or therapeutic targets, which can have major clinical impact [2]. Several studies have shown that targeting various molecular alterations of interest in specific tumor types can improve outcomes, including EGFR, ALK, ROS1 or BRAF V600E in non-small-cell lung cancer [5–8], BRAF V600E in melanoma [9], BCR-ABL in chronic myeloid leukemia [10], or RET in medullary thyroid cancer [11]. Cancer therapies targeting actionable molecular alterations (AMA) have developed, but the clinical routine impact of high-throughput molecular profiling remains unclear. Methods: Patients included had solid cancer and underwent cfDNA genomic profiling with FoudationOne Liquid CDx (F1LCDx) test, analyzing 324 genes. No notable benefit in patient’s outcomes was shown in this unselected pan-cancer study
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