Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with the 2019 ASCO Annual Meeting but not presented at the Meeting, can be found online only.
Initiation of targeted therapy based on ctDNA only in metastatic NSCLC.
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr e20687)
Author(s): Jean Gabriel Bustamante Alvarez, Kristin Dittmar, Sarah A Janse, Stephanie Kiourtsis, Dwight Hall Owen, Erin Marie Bertino, Kai He, David Paul Carbone, Gregory Alan Otterson; Albert Einstein Medical Center, Philadelphia, PA; The Ohio State University, Columbus, OH; Division of Medical Oncology, Department of Internal Medicine, Ohio State University, Columbus, OH; The Ohio State University Comprehensive Cancer Center, Columbus, OH
Background: Next generation sequencing (NGS) of circulating tumor DNA (ctDNA) can identify sensitizing and resistance mutations in Non-Small Cell Lung Cancer (NSCLC). ctDNA is helpful when tissue is insufficient for genomic testing, or repeat biopsy is undesirable. Here we report a single institution experience of ctDNA testing on diagnosis (DX) and progression (PD), and how this intervention can help avoid further invasive interventions and warrant change in management. Methods: This is a single institution retrospective study of advanced NSCLC patients (pts) who had ctDNA from plasma tested using Guardant360, which identifies somatic genomic alterations by massively parallel sequencing of target genes. An institutional CLIA tissue panel using FISH (for MET, RET, ROS1 and ALK) and NGS for selected genes was used for tissue analysis. Actionable mutations are those with FDA approved (EGFR, ALK, ROS, BRAF) or NCCN recommended targeted therapies (RET fusions and MET amplifications or MET Exon 14 skipping mutation). All the included patients had cancer confirmed by pathology analysis. IRB approval was obtained prior to data collection. Results: A total of 163 ctDNA samples from 143 pts were evaluated (82 at DX and 81 on PD) . 17 out of 82 (20.7%) ctDNA samples sent at DX had actionable mutations identified (4 EGFR exon 19 deletion, 2 EGFR Exon 21 L858R, 1 EGFR L861R, 4 EML4-ALK Fusion, 2 CD74-ROS1 Fusion, 2 MET exon 14 skipping mutation, 2 KIF5B-RET fusion). 7 out of 82 (8.5%) pts initiated targeted therapy based on ctDNA results only (5 with no or insufficient tissue available, 2 with negative tissue analysis). Among them, 1 CR, 5 PR, and 1 SD were achieved. For the 2 pts with negative tissue analysis , one had initial PR for 4 months with crizotinib and on progression tissue rebiopsy was positive for ALK rearrangement on FISH, for L1152R on NGS and on ctDNA for EML4-ALK Fusion, ALK G1202R and L1152P. On second line this patient achieved a near CR with Carboplatin/Pemetrexed/Pembrolizumab. The second patient with negative tissue had CD74-ROS1 fusion on ctDNA and achieved a CR with crizotinib for 8 months. The Response Rate for patients started on targeted therapies based on ctDNA only was 85%. Conclusions: A substantial number of NSCLC pts benefited from targeted ctDNA NGS by identifying actionable mutations that led to appropriate targeted treatments. Initiation of targeted therapy for advanced NSCLC was possible based on ctDNA testing only .