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L.D.C. Castillero
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P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.02-004 - Analysis of MET in Liquid Biopsy and Tissue Biopsy in Patients with Advanced NSCLC: Incidence and Pattern. (ID 8726)
09:30 - 09:30 | Author(s): L.D.C. Castillero
- Abstract
Background:
MET pathway is dysregulated in several cancers, having three types of alterations: overexpression, amplification and mutation. MET amplification has been reported in 2-4% of NSCLC while MET exon 14 skipping mutation has been found in 3-4% of lung adenocarcinoma. Increased MET expression is associated with higher malignancy, and acts as a negative prognostic factor. To date, several MET inhibitors are in development. Hence, the importance of understanding MET biology, its incidence, patterns of appearance, and which type of genomic abnormality. Is MET a trunchal genomic abnormality or does it appear as a result of mechanism of resistance of tumor cells once exposed to therapeutic agents? In the past, MET inhibitors have failed to improve OS in clinical trials; lack of benefit from this approach was the fact that there was no standard method for detecting MET related anomalies that allowed an adequate patient (pt) selection.
Method:
A search for MET alterations was performed in a retrospective analysis from November 2014 until May 2017. A total of 142 liquid biopsies (LBx) from pts with advanced NSCLC using NGS were identified. Once pts with a MET genomic alteration were identified by LBx, we proceed to review their initial tumor biopsy (TBx) genetic analyses and assess for the presence of MET alterations. Data regarding histologic subtypes, therapy received in each case, and timing of LBx analysis were collected.
Result:
A total of 142 LBx were identified in our cohort of patients with advanced NSCLC from November 2014 until May 2017. These samples came from 127 pts; 20 pts (15.7%) had MET alterations identified by LBx. Characteristics of these 20 pts were: median age was 72 (range, 62-85); 15 pts (75%) were females; all patients had adenocarcinoma histology. Genomics alterations in LBx were distributed as: 5 amplifications and 15 mutations. Genetic analyses from the TBx of these 20 pts done at initial diagnosis were reviewed. There were 8 pts who had TBx and LBx done at the same time and at initial diagnosis; only 2 pts out of these 8 had MET alterations in both tests (amplifications). The other 6 pts (with both TBx and LBx done simultaneously) had MET alterations identified only by LBx despite other genetic abnormalities concordance found between TBx and LBx in 5/6 pts. In these pts, median number of alterations identified by LBx and TBx were 7 and 0.5, respectively. There were 12 pts who had LBx done after progression of disease. All these pts had MET alterations identified in LBx however, none of them had MET genomic abnormalities in their TBx at initial diagnosis. One pt who had MET exon 14 skipping mutation in LBx (at progression of disease) did not have TBx genetic analysis due to insufficient tumor tissue.
Conclusion:
In this pt sample, we were able to identify more sensitivity from LBx than TBx for detection of MET alteration at initial diagnosis when both tests were done simultaneously. Our pts had metastatic disease with lesions outside the lung parenchyma. This will increase the diagnostic yield of LBx. Also, tumor heterogeneity plays a major role for discrepancies between TBx and LBx. The median number of genomic alterations identified by LBx was also higher than the one reported by TBx. Interestingly, 12 pts with MET alterations at progression of disease did not have these anomalies at TBx (initial diagnosis). Many questions remain unanswered. A prospective clinical trial using NGS in both tissue and blood at initial diagnosis will help us to identify and understand the biology of MET. It seems that LBx could be a complimentary tool at initial assessment of pt with metastatic NSCLC.
