1249P - cMET expression and activity of first-line erlotinib in advanced non-small cell lung cancer (NSCLC) patients (pts): exploratory analysis of the ran...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Translational Research
Presenter Ming Tsao
Citation Annals of Oncology (2014) 25 (suppl_4): iv426-iv470. 10.1093/annonc/mdu349
Authors M. Tsao1, M. Di Maio2, L. Kim3, G. Liu4, J. Xu3, V. Gebbia5, M.A. Burgio6, Z.Y. Alam7, G. Valmadre8, B. Higgins9, S. Signoriello10, A. Rossi11, N. Leighl4, P. Maione11, C.A. Butts12, F. Ciardiello13, R. Feld4, C. Gallo10, C. Gridelli14, F. Perrone2
  • 1Pathology Department, Princess Margaret Cancer Centre, ON M5G 2M9 - Toronto/CA
  • 2Clinical Trials Unit, Istituto Nazionale Tumori – I.R.C.C.S - Fondazione Pascale, 80131 - Napoli/IT
  • 3Pathology Department, Princess Margaret Cancer Centre, Toronto/CA
  • 4Medical Oncology, Princess Margaret Hospital, Toronto/CA
  • 5Medical Oncology Unit, La Maddalena Clinic for Cancer, Palermo/IT
  • 6Medical Oncology, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), Meldola, 47014 - Meldola (FC)/IT
  • 7Medical Oncology, Windsor Regional Cancer Centre, Windsor/CA
  • 8Dept. Of Internal Medicine And Hematology, Ospedale E. Morelli AOVVAzienda Ospedaliera Valtellina e Valchiavenna, IT-23039 - Sondalo/IT
  • 9Medical Oncology, Peel Regional Cancer Centre, Credit Valley Hospital, Mississauga/CA
  • 10Medical Statistics, Second University, Napoli/IT
  • 11Medical Oncology, Azienda Ospedaliera S. Giuseppe Moscati, Avellino/IT
  • 12Department Of Oncology, University of Alberta Cross Cancer Institute, T6G 1Z2 - Edmonton/CA
  • 13Dip. Medico Chirurgico Di Internistica, Seconda Università Studi di Napoli Policlinico Federico II, 80131 - Napoli/IT
  • 14Medical Oncology, Azienda Ospedaliera S. Giuseppe Moscati, 83100 - Avellino/IT

Abstract

Aim

In the TORCH trial, molecularly unselected pts with advanced NSCLC were randomized to erlotinib (E) or cisplatin + gemcitabine (CG) as first line within planned treatment sequences. Several biomarkers were studied with exploratory aim. Here we report cMET and PTEN data.

Methods

cMET and PTEN immunohistochemistry (IHC) was performed using standard method and SP44 (Ventana) and 138G6 (Cell Signaling) antibodies, respectively. H-score (intensity x % stained tumor cells) was used to classify cMET IHC (<200) low vs high (≥200) cases. PTEN was scored as IHC- (complete absent) vs IHC+ (any staining). Out of 760 pts in the TORCH study, IHC result was available in 155 for cMET and 148 for PTEN. Interaction between biomarker expression and treatment outcome was tested by Cox model for progression-free survival (PFS) and by Zelen exact test for response rate (RR).

Results

PTEN was positive in 118 pts (80%). PTEN showed no significant interaction with treatment and did not vary between EGFR mut+ and wildtype (wt). cMET was high in 92 pts (59%). As for PFS, HR (E vs CG) was 1.22 (95% CI 0.71-2.07) in cMET low and 2.81 (95% CI 1.79 – 4.41) in cMET high (interaction p = 0.013); in the E arm, HR for cMET low vs cMET high pts was 0.45 (95% CI 0.27-0.74). Response rate (RR) to E/CG was 21%/17% in cMET low vs 0%/24% in cMET high (interaction p = 0.005). The RR difference within the E arm was statistically significant (p = 0.002). cMET was high in 76% (16/21) of EGFR mut+ pts and 58% (76/132) of EGFR wildtype (wt) pts (p = 0.11). Among EGFR wt pts, PFS HR (E vs CG) was 1.65 (95% CI 0.95-2.89) in cMET low and 3.25 (95% CI 1.95 – 5.42) in cMET high (interaction p = 0.07). In the E arm, HR for cMET low vs cMET high was 0.49 (95% CI 0.29-0.83). RR to E/CG was 14%/19% in cMET low vs 0%/21% in cMET high (interaction 0.07). The RR difference within the E arm was statistically significant (p = 0.03). Numbers were too small to test interaction in EGFR mut+ pts.

Conclusions

In pts unselected for EGFR mutation and in those with EGFR wt, the relative effect on PFS of E vs CG is less worse among low cMET cases. Objective responses to first line E were only reported among low cMET cases, even if EGFR wt.

Disclosure

M. Tsao: received honoraria on this subject matter from: Roche, AstraZeneca, and received a research grant from Roche; M. Di Maio: acted as consultant or advisory role for Eli Lilly and received honoraria from Eli Lilly and Roche; A. Rossi, P. Maione and C. Gridelli: acted as consultant for Eli Lilli, Roche and received honoraria from Eli Lilli, Roche; C.A. Butts: acted as consultant for Roche and received honoraria from Roche; R. Feld: acted as consultant for Roche, received honoraria from Roche and received a research grant from Roche; F. Perrone: received honoraria from Roche and received a research funding from Roche. All other authors have declared no conflicts of interest.