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
Presenter Rafael Rosell
Authors 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
  • 1Medical Oncology Service, Catalan Institute of Oncology ICO Badalona Hospital Germans Trias i Pujol, Medical Oncology, 08916 - Badalona/ES
  • 2Medical Oncology, Hospital General Universitario de Alicante, ES-03010 - Alicante/ES
  • 3Laboratoy Of Biology Department, Pangaea Biotech, USP Dexeus University Institute, 08028 - Barcelona/ES
  • 4Oncology, Instituto Oncologico Dr Rosell, USP Dexeus University Institute, 08028 - Barcelona/ES
  • 5Oncology, Drum Tower Hospital, 210008 - Nanjing/CN
  • 6Service De Pneumologie, Hopital du CluzeauCHU Dupuytren, FR-87042 - Limoges CEDEX 1/FR
  • 7Pathology, Brigham and Women's Hospital / Harvard Medical School, 02115 - Boston/US
  • 8Medical Oncology, Dana-Farber Cancer Institute, 02115 - Boston/US
  • 9Hematology/oncology, University Of California, UCSF Diller Comprehensive Cancer Center, UCSF Box 2140 - San Francisco/US
  • 101 Unità Operativa Di Pneumologia Oncologica, Azienda Ospedaliera S. Camillo Forlanini, IT-00151 - Rome/IT
  • 11Oncologia Médica, Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 12Pneumology, Centre François Baclesse, Caen/FR
  • 13Medical Oncology, University of Messina, Messina/IT
  • 14Oncology, Hospital de Sant Pau, 08025 - Barcelona/ES
  • 15Oncology, Catalan Institute of Oncology, 17007 - Girona/ES
  • 16Oncology, Complejo Hospitalario Universitario A Coruña, 15006 - A Coruña/ES
  • 17Hospital Universitario Virgen del Rocio, 41013 - Sevilla/ES

Abstract

Background: 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.