1311P - Next generation sequencing (NGS) reveals qualitative and quantitative molecular heterogeneity within EGFR-mutant advanced lung adenocarcinoma (ALA)...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Pathology/Molecular Biology
Translational Research
Presenter Emilio Bria
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors E. Bria1, S. Pilotto1, E. Amato2, M. Fassan2, S. Novello3, U. Peretti1, T. Vavala3, S. Kinspergher1, L. Righi3, A. Santo4, I. Sperduti5, M. Milella6, A. Scarpa7, G. Tortora8
  • 1Medical Oncology, Azienda Ospedaliera Universitaria Integrata Verona-"Borgo Roma", 37134 - Verona/IT
  • 2Pathology, ARC-NET Applied Research on Cancer Center, 37134 - Verona/IT
  • 3Department Of Clinical And Biological Sciences - Thoracic Oncology Unit, Azienda Ospedaliero-Universitaria ASOU San Luigi Gonzaga, 10043 - Orbassano/IT
  • 4Medical Oncology, Azienda Ospedaliera Universitaria Integrata Verona-"Borgo Roma", 37129 - Verona/IT
  • 5Biostatistics, Regina Elena National Cancer Institute, 00144 - Roma/IT
  • 6Divisione Di Oncologia Medica A, Istituto Nazionale Tumori Regina Elena, 00144 - Roma/IT
  • 7Patologia E Diagnostica, Anatomia Patologica, Azienda Ospedaliera Universitaria Integrata Verona-Borgo Roma, 37134 - Verona/IT
  • 8Oncologia Medica, Azienda Ospedaliera Universitaria Integrata Verona-"Borgo Roma", 37134 - Verona/IT

Abstract

Aim

Despite striking G efficacy in EGFR-mut ALA, approximately 25% of pts rapidly progress during treatment. Thus, we used NGS to assess whether molecular heterogeneity may help better predict ultimate pts' outcome.

Methods

EGFR-mut ALA pts receiving 1st line G were retrospectively grouped into poor (Cohort A: progression at 1st assessment), intermediate and good responders (Cohorts B and C: progression within and after 12 mos). Clinical outcome was correlated with: 1) the Rate of EGFR-Mut Cells (RMC); 2) Additional Coexisting Mutations (ACM), using NGS (Ion Lung Colon Cancer Panel, Life Technologies).

Results

18 pts were gathered (M/F 6/12, median age 72 yrs, PS 0/1 14/4, del19/L858R 13/5, progressions/deaths 14/7). Median PFS was 1.7 (95% CI 0.1-3.2), 6.1 (95% CI 3.0-9.2) and 17.3 mos (9.0-25.5) for cohorts A, B and C (n = 6, 3 and 8, respectively; p < 0.0001). Cohort A had significantly more smokers (66.7% vs 10.0%, p = 0.04). Median PFS and OS were longer in pts with RMC ≥36.6% (12.0 vs 4.0 mos, p = 0.31; not reached vs 18 mos, p = 0.59); moreover, RMC distributed differently in the 3 cohorts with a trend towards higher RMC in cohort C (35.1% versus 21%, p = 0.08). Fourteen ACM were found: TP53 (7 pts), KRAS (2 pts), CTNNB1 (2 pts), PIK3CA, SMAD4 and MET in 1 pt. TP53 mutations were exclusively documented in cohorts A and B (66.7% versus 0%, p = 0.009). ACM significantly affected both PFS (median 3 vs 12.3 mos, p = 0.03, for pts w or w/o ACM, respectively; HR 2.88, 95% CI 0.92-9.02, p = 0.068) and OS (3.6 mos vs not reached, p = 0.03; HR 5.07, 95% CI 0.99-26.03; p = 0.052). TP53 was the strongest negative modifier (median PFS 4 vs 14 mos, p = 0.03, for pts w or w/o TP53 mutations; HR 4.66, 95% CI 1.12-19.37, p = 0.03). Pts with a RMC ≥ 36.6% and no ACM fared significantly better than the others (median PFS 17.3 vs 3 mos, p = 0.03, respectively; HR 3.26, 95% CI 0.78-10.85, p = 0.054), with a trend towards increased OS (median: not reached vs 4 mos, p = 0.06; HR 4.01, 95% CI 0.78-20.59, p = 0.10).

Conclusions

NGS of EGFR-mut ALA receiving 1st line G reveals quantitative (RMC) and qualitative (ACM) molecular heterogeneity, which may explain different individual outcomes.

Disclosure

All authors have declared no conflicts of interest.