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E. Sensi
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-034 - Clinical Impact of Pretreatment EGFR T790M Mutation in Lung Adenocarcinoma Patients (ID 5463)
14:30 - 14:30 | Author(s): E. Sensi
- 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.
