LBA31 - Concomitant actionable mutations and overall survival (OS) in EGFR-mutant non-small-cell lung cancer (NSCLC) patients (p) included in the EURTAC tri...
|Date||01 October 2012|
|Event||ESMO Congress 2012|
|Session||NSCLC metastatic, II|
R. Rosell1, B. Massuti Sureda2, C. Costa3, M.A. Molina3, A. Gimenez-Capitan3, N. Karachaliou4, J. Wei5, A. Vergnenegre6, P. Giannikopoulos7, C. Mermel8, T. Bivona9, F. De Marinis10, E. Felip11, M.T. Moran Bueno1, R. Gervais12, M. Santarpia13, M. Majem14, J. Bosch-Barrera15, M.R. Garcia-Campelo16, L. Paz-Ares17
AbstractBackground: At the final cutoff of April 2012, in the randomized phase III EURTAC trial, erlotinib improved progression-free survival (PFS) in comparison with chemotherapy as first-line treatment in European p with EGFR-mutation-positive NSCLC (HR, 0.34; P < 0.0001). No differences were observed in overall survival (OS)
(22.9 vs 20.8 months [m]).
Methods: We have assessed EGFR T790M and TP53 mutations, the EML4-ALK translocation and BIM mRNA expression in pretreatment tumor samples of 95 p from the EURTAC trial and correlated our findings with outcome.
Results: Concomitant T790M was found in 37.89%, TP53 in 24.21% and EML4-ALK in 15.8% of p. BIM expression was low or intermediate in 55.8% of p and high in 31.6%. 86.7% of the 45 p receiving chemotherapy had crossed over to receive EGFR
TKIs at the time of progression. In p treated with erlotinib, overall response rates (ORR) were 87.5% in p with high BIM expression and 34.6% in p with low/ intermediate BIM; ORR in the chemotherapy group were 11.1 and 14.2, respectively (P = 0.0002). Among p in the erlotinib group without T790M mutations, ORR was 100% for p high BIM expression vs 35.2% for p low/intermediate BIM levels
(P = 0.01). In the multivariate analysis, only erlotinib (HR, 0.36; P < 0.0001) and high BIM expression (HR, 0.55; P = 0.03) were markers of longer PFS. OS for p with T790M mutations was 40.1 m in p with high BIM levels and 15.4 m in p with low/ intermediate BIM levels (P = 0.04). In the multivariate analysis, including T790M, TP53 and EML4-ALK, only high BIM expression emerged as a marker of longer OS (HR, 0.47; P = 0.02).
Conclusions: Our results can lead to the design of studies of treatment based on the presence of the EGFR T790M mutation and BIM expression levels. We are currently designing a clinical trial based on our findings.
Disclosure: All authors have declared no conflicts of interest.