Analysis of circulating tumor cells ( CTCs) and circulating cell-free DNA (cfDNA), detected in peripheral blood of patients, is an extraordinary novel strategy to identify and study NSCLC patients, in order to obtain prognostic and predictive molecular informations with a simple, non invasive and sensitive method. Liquid biopsy therefore offers a new source of cancer cells and cancer-derived materials in order to test more personalized treatment. With two PCR-based next generation sequencing (NGS) approaches we evaluated 45 patients with not squamous NSCLC ; in eighteen pts ( 40 % ) almost one genomic mutation was detected among 56 different genes analyzed with NGS. Median age of patients was 69 years ( 55-78) and 14 (73%) were males. Altogether, 11 genes were mutated with a panel of 56 genes analyzed (19,6% ) . The most frequent mutations occurred in KRAS, TP53, MET,KDR, KIT, SMAD4 and MET genes. Several patients expressed many mutations and the most frequent detected concerned gen c-Kit ( 22%). Other mutations concerned the following genes : TP53 ( 16 % ), MET/KDR. / SMAD4/KRas ( 44%). Other genomic alterations concerned the following genes: JACK3 (5%); APC(5%); ERBB4(5%); CTNNB! (5%); EGFR (5%). Altogheter the response to therapy was higher among patients with mutation of Smad 4 gene and lower in patients with mutations of KIT gene. All side effects occurred with target therapy was categorized according to the Common Terminology Criteria for Adverse Events, 4.0 version. An increase of gastroenteric (G3/G4) and hematologic toxicity (G3/G4) was observed in patients with Kit mutations. In our study this correlation was observed mainly during treatment with Tyrosine Kinase Inhibitors (TKIs ).Evaluating Progression Free Survival (PFS) in all the patients recruited in the study, a median PFS of 12.5, 11.5, 4 and 9 months was observed respectively in patients with mutations of KIT, SMAD4, TP53 and MET. In this study, all the genetic alterations analyzed and highlighted were related to the response to chemotherapeutic treatments and possible tyrosine kinase inhibitory treatments in terms of PFS and toxicity.

Note: This abstract was not presented at the meeting.

Citation Format: Silverio Tomao, Monica Verrico, Luigi Rossi, Iacobelli Stefano. Predictive therapeutic value of NGS with liquid biopsy in metastatic NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3334.