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MA 11 - Emerging Diagnostic/Biomarkers in NSCLC (ID 668)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Advanced NSCLC
- Presentations: 1
MA 11.01 - Liquid Biopsies for Monitoring BRAF Mutation (V600E) in Advanced BRAF (V600E) Non-Small Cell Lung Cancer (NSCLC) (ID 10232)
11:00 - 12:30 | Author(s): C. Jovelet
Circulating tumor DNA (ctDNA) has been shown beneficial in monitoring EGFR mutations in blood, especially for the detection of resistance mutations, like T790M in NSCLC patients. However, the role of BRAF (V600E) ctDNA for monitoring the patient’s response has not been studied yet. The aim of this study was to determine the clinical relevance of BRAF (V600E) ctDNA for monitoring the response to BRAF inhibitors in a prospective cohort of advanced NSCLC BRAF (V600E) patients.
We prospectively enrolled advanced NSCLC patients with BRAF (V600E) treated with BRAF +/- MEK inhibitors in our institution. A blood sample was collected at different time points, including at baseline, during treatment and at progressive disease. ctDNA BRAF analysis was performed using the Inivata InVision platform (enhanced tagged-amplicon next-generation sequencing (eTAM-Seq).
Between June 2016 and June 2017, 14 patients have been included. Eight patients (57%) were females, 9 (64%) non-smokers, with a median age of 63 years (35-70). All the patients had adenocarcinoma and BRAF (V600E) mutation in tissue analysis. Thirteen patients (93%) had stage IV at diagnosis, 7 patients (50%) with bone, 6 (43%) pleural and 4 (29%) lung metastasis. The median of lines of treatment received was 2 (1-4). Thirteen patients (93%) received BRAF + MEK inhibitor and 1 patient (14%) BRAF inhibitor, with an objective response rate of 64% (1 complete, 8 partial response) and disease control rate of 86%. BRAF mutation detection was tested under treatment in 12 patients (86%). Longitudinal analysis was performed from the serial sampling in 6 patients to date: 4 patients (67%) were ctDNA positive for BRAF (V600E) at time of progression, with a range of allelic frequency of 0.11-6.16%. BRAF mutation was not detectable in patients with objective response (2/6, 33%) at time of sample collection(s). Additional BRAF (V600E) NSCLC patient samples are being analyzed.
Liquid biopsy for monitoring BRAF (V600E) using ctDNA appears to be feasible and useful in advanced NSCLC patients. Updated longitudinal results for the complete patient cohort will be presented at the meeting.
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P1.03 - Chemotherapy/Targeted Therapy (ID 689)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
P1.03-013 - Monitoring of ALK Fusions and Mutations in Advanced ALK Positive Non-Small Cell Lung Cancer (NSCLC) Patients (ID 10208)
09:30 - 16:00 | Author(s): C. Jovelet
Co-isolated exosomal RNA and cfDNA from plasma can be used for detection of genomic alteration such as EML4-ALK fusion RNA and ALK resistance mutations in NSCLC patients. The clinical utility of this liquid biopsy for response monitoring is under investigation. The aim of this study was to evaluate liquid biopsy as tool for monitoring response to treatment in a prospective cohort of ALK-positive NSCLC patients.
Consecutive ALK positive NSCLC patients treated with systemic therapies in our institution were enrolled. After informed consent, blood samples were prospectively collected for longitudinal analysis during treatment and at progression. Exosomal RNA and cfDNA co-isolated from plasma was used for detection of EML4-ALK fusion RNAs by the qPCR-based ExoDx Lung(ALK)™-test as well as for analysis of ALK-resistance mutations by ExoDx NGS sequencing.
From Aug 2016 to date, 23 patients were enrolled in the study, 14 (61%) were females, 15 (65%) non-smokers, median age of 50 years (23-76). All patients had adenocarcinoma and were tissue positive for ALK by immunohistochemistry 14 (61%) and/or FISH 16 (70%). Nineteen patients (83%) had stage IV disease at diagnosis, with brain involvement in 7 patients (37%), bone in 11 (48%) and liver in 2 (11%). The median number of ALK inhibitors received was 2 (0-4). Twenty-one patients (91%) received ALK inhibitors (5 crizotinib, 3 ceritinib, 13 next-generation inhibitors) and 2 chemotherapy, with an objective response rate of 48%. Five out of 8 patients (63%) that were treatment naïve (baseline) or progressive disease (PD) at the time of collection, were positive for EML4-ALK by liquid biopsy, 1 of 4 samples (25%) at baseline, and 4 of 4 samples (100%) at PD, were positive by liquid biopsy. EML4-ALK variant 1 was detected in two (40%) and variant 3 in three patients (60%). All 26 samples collected during objective response or stable disease (100%) were negative for EML4-ALK by liquid biopsy. The ALK resistance mutation panel was performed on 2 samples from patients with PD, and both were detected positive for ALK resistance mutations, L1196M (variant 1) and G1202R (variant 3), respectively.
The monitoring of ALK fusions on exosomal RNA by liquid biopsy is applicable in the clinic and closely correlated to disease control. ALK mutations detection using liquid biopsy can be an accurate tool for assessing the resistance to ALK inhibitors. Updated results from up to 30 patients will be available for the final presentation.