Virtual Library
Start Your Search
G. Alì
Author of
-
+
P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
-
+
P3.02b-027 - Detection of EGFR Mutations in Plasma of Lung Adenocarcinoma Patients Using Real-Time PCR and Mass Spectrometry (ID 5475)
14:30 - 14:30 | Author(s): G. Alì
- Abstract
Background:
Lung adenocarcinoma patients harbouring sensitizing EGFR mutations can benefit from treatment with tyrosine kinase inhibitors (TKI). Whenever tumour tissue is inadequate or unavailable, detection of EGFR mutations in circulating cell-free tumour (ct) DNA from plasma is crucial to predict and monitor response to therapy. In this study we compared EGFR status between tumour tissue and plasma, using real-time PCR. Moreover, we evaluated the adequacy of ctDNA for a multi-target mass spectrometry (MS) analysis.
Methods:
EGFR mutations were investigated in paired plasma and tumour tissues from a prospective series of 105 lung adenocarcinoma patients: 79 had no prior TKI treatment and 26 underwent re-biopsy for TKI-acquired resistance. Molecular analyses were performed on tissue by a routine MS test (evaluation of 307 hot-spots in 10 genes including EGFR) and on ctDNA by a validated Scorpion/LNA real-time PCR (evaluation of 30 EGFR mutations). In the 26 postTKI patients ctDNA analysis was performed also by MS.
Results:
1-Plasma versus tissue by real-time PCR: overall sensitivity, specificity and concordance were 64.8%, 95.4% and 82%. In preTKI patients, 17 harboured EGFR sensitizing mutations on tissue,10 detected also in plasma (sensitivity 58.8 %, specificity 100%, concordance 91%). All 26 postTKI patients preserved EGFR sensitizing mutations. Regarding the detection of EGFR T790M resistance mutation, sensitivity, specificity and concordance were 63.6%, 80% and 73%. Specifically, 11 patients were T790M-positive (42%): 7 on both specimens, 4 only on tissue and 3 only on ctDNA. 2-Plasma versus tissue by MS: sensitivity, specificity and concordance for T790M were 50%, 93.3% and 76%. Particularly, 6 patients had a T790M-positive ctDNA: 5 concordant and 1 discordant with tissue; 4 T790M-positive cases on tissue were undetected in plasma; 1 sample was not evaluable.
Conclusion:
The real-time PCR on ctDNA showed a sensitivity consistent with literature and a high specificity, mostly in preTKI group. Concordance rates, influenced by biological and methodological factors, were lower in postTKI group. Indeed, some T790M mutations were detected only on ctDNA, which is expected to effectively mirror tumour heterogeneity better than bioptic samples, thus giving a global view of tumour. Finally, we demonstrated the adequacy of ctDNA for MS, in terms of quantity and quality. The use of a multi-target analysis on ctDNA might improve tumour characterization and response monitoring, evaluating important oncogenes other than EGFR, like PIK3CA, KRAS and BRAF. However, further studies are needed to better explore MS applicability on ctDNA.
-
+
P3.02b-034 - Clinical Impact of Pretreatment EGFR T790M Mutation in Lung Adenocarcinoma Patients (ID 5463)
14:30 - 14:30 | Author(s): G. Alì
- Abstract
Background:
About a half of lung adenocarcinoma patients with an activating EGFR mutation undergoing tyrosine kinase inhibitor (TKI) therapy develop the EGFR T790M resistance mutation. Previous studies have reported that T790M positive clones are already present before the TKI treatment in the 0.32-80% of cases, depending on methodology and population. Whereas a statistical association between the presence of pretreatment T790M and the L858R activating mutation has been demonstrated, little is known about the influence of preexisting T790M clones on the clinical outcome. The aim of our study is to investigate whether pretreatment T790M affect the response to TKIs.
Methods:
We selected 18 patients who developed a T790M-related resistance to TKI therapy. Their sensitizing mutations were L858R or exon 19 deletion in 8 and 10 cases respectively. For all patients pre- and post-treatment tumor tissues were available to detect and quantify T790M mutant alleles with a highly sensitive digital PCR analysis (Raindance Technologies).
Results:
Pretreatment T790M was found in 5 out of 18 patients (28%), with a mutation frequency ranging from 0.03% and 0.14% (mean frequency 0.08%). The mean T790M allele frequency in posttreatment tumors was 12%. The presence of T790M before TKIs was not associated with a specific activating mutation (L858R or exon 19 deletion), nor with the disease stage and worse response to treatment, independently from the type of TKI drug.
Conclusion:
Our results confirm that T790M-positive clones can coexist with the activating mutation clones in lung adenocarcinoma even before TKI treatment. A previously reported analysis, performed with a methodology as much sensitive as ours by Watanabe et al., showed a pretreatment T790M mutation frequency raising the 80% in a series of lung adenocarcinoma patients harboring an EGFR activating mutation, with no regard to TKI treatment or resistance. In contrast, we found 28% of cases having T790M before treatment. This discrepancy can be due to the different criteria adopted for samples selection, since our cohort included only patients found positive for T790M after TKI therapy. In our series of cases, the presence of T790M before TKIs did not correlate with significant clinical parameters. In conclusion, in this preliminary study we did not identify a direct association between the presence of small amounts of pre-TKI T790M mutant alleles and patients’ clinical outcome. However, in order to better assess the impact of T790M in predicting the response to therapy, further studies on larger series of patients are needed.
