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Valentina Bertaglia



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    P2.14 - Targeted Therapy (ID 183)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.14-17 - Correlation Between Clinic-Pathological Data and T790M Detection in EGFR Mutated NSCLC Patients Progressing on 1st/2nd Generation TKIs (Now Available) (ID 2442)

      10:15 - 18:15  |  Author(s): Valentina Bertaglia

      • Abstract
      • Slides

      Background

      Despite osimertinib is moving to the first-line for advanced NSCLC harboring EGFR activating mutations, some patients still receive a frontline first- or second-generation EGFR-TKI. In this setting, factors predicting the emergence of T790M resistance mutation at progression (PD) are lacking. The aim of this retrospective study was to investigate the correlations between clinic-pathological features and T790M positivity (T790M+) in a single-center cohort of EGFR mutated stage IV or recurrent NSCLC patients, who underwent liquid (LB) or tissue biopsy (TB) at PD when treated with first- or second-generation EGFR-TKIs.

      Method

      Data from 122 patients (80 female, 42 male) treated between 2012 and 2019 were considered for the analysis. EGFR mutations were detected with real time-polymerase chain reaction (RT-PCR) on LB and pyrosequencing or next generation sequencing on TB. PD was determined by RECIST 1.1 criteria. Univariate analysis by Fisher exact test was performed to assess any association.

      Result

      At diagnosis, 117 patients carried common EGFR mutations (84 exon 19 deletions; 33 exon 21 mutations), 5 had rare mutations (3 exon 18 mutations; 2 exon 20 mutations other than T790M) . At PD, 29 patients (24%) underwent only LB, 29 only TB (24%), 64 both (52%). The overall T790M+ rate was 67% (82/122). T790M+ was significantly higher among patients with exon 19 deletion than in those with exon 21 mutation (77% vs 51%, p=0.008). T790M+ was significantly more frequent in patients with exclusively intrathoracic PD as compared to extrathoracic PD (81% vs 56%, p=0.007). Patients with pleural involvement (PI), considered as pleural effusion or/and pleural disease, as site of PD (n=45) had a significantly higher frequency of T790M+ than those with stable or absent PI (n=77) (82% vs 58%, p=0.009), irrespectively of the pattern of PD. No correlation with other sites of PD was found.

      Conclusion

      Exon 19 deletion, intrathoracic PD and PI as site of PD are significantly associated with higher frequency of T790M+ in patients progressing to first-or second-generationEGFR-TKIs. These results, if confirmed by an independent validation cohort, may allow the development of a T790M+ predictive score accounting for type of mutation and sites of progression.

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