The following article features coverage from the European Society for Medical Oncology (ESMO) 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Thirty-four potentially “druggable” genomic targets were identified in a cohort of patients with advanced NSCLC who underwent plasma-based DNA sequencing, according to results of a study presented at the European Society for Medical Oncology (ESMO) Congress 2019 held in Barcelona, Spain.

Potential advantages of next-generation sequencing (NGS) of circulating tumor cell-free DNA (ctDNA) over tumor tissue-based NGS include ease of sampling, as well as the potential to evaluate for tumor heterogeneity. 

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Although the use of plasma-based NGS for the diagnosis and treatment of patients with advanced NSCLC (aNSCLC) has become integrated into routine clinical practice, randomized clinical trial evidence regarding the clinical impact of using it as either a standalone test or in conjunction with tissue-based NGS are still lacking. 

In this study, consecutive patients with aNSCLC characterized by wild-type EGFR, ALK, and ROS1 based on prior standard genomic testing were prospectively screened using either a 73-gene ctDNA assay (METex14 Guardant360) or a 59-gene tissue-based next-generation sequencing (METex Oncomine Focus Assay), or both. All identified genomic alterations classified as “druggable” were verified using another method. 

Of the 159 patients included in the study, approximately three-quarters were current/former smokers and 91% had disease characterized by adenocarcinoma histology.  Within this cohort, ctDNA sequencing results were available for 129 (81%) patients, and both ctDNA and tumor tissue sequencing were available for 63 patients (49%). 

The median number of genomic alterations detected using ctDNA NGS was 2, with 17 representing the highest number of alterations found in a single sample. 

Notably, 34 druggable genomic alterations were detected in the samples analyzed by ctDNA sequencing, although results for 3 of these were discordant with tumor tissue-based DNA sequencing.

In the subgroup of patients with 1 or more druggable genomic alteration(s) on plasma-based sequencing, 12 underwent treatment with targeted therapy; disease control was observed in 5 of the 6 patients in this subgroup for whom radiologic assessment was performed. 

Of the 18 patients with 1 or more detectable druggable alteration who had received prior treatment with immunotherapy, an objective response to treatment was observed for only 2 patients – one with disease characterized by a METex14 mutation and the other defined as RET rearrangement-positive aNSCLC. Furthermore, no objective responses to immunotherapy were observed in patients with dual KRAS-STK11 mutations who had received this treatment (3 patients).

In their concluding remarks, the study authors noted the apparent feasibility of using plasma-based NGS in the setting of aNSCLC, as well its potential ability to predict response to immunotherapy in some patients with this disease.

Read more of Cancer Therapy Advisor‘s coverage of the ESMO annual meeting by visiting the conference page.

Reference

Bonanno L, Pavan A, Ferro A, et al. Clinical impact of plasma next-generation sequencing (NGS) in advanced non-small cell lung cancer (aNSCLC). Presented at:  European Society for Medical Oncology (ESMO) Congress 2019; September 27-October 1, 2019: Abstract 1414P.