196P - Prevalence, prognostic significance, and overlap of actionable biomarkers in NSCLC

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Lung and other Thoracic Tumours
Personalised Medicine
Translational Research
Presenter David Shames
Citation Annals of Oncology (2014) 25 (suppl_4): iv58-iv84. 10.1093/annonc/mdu326
Authors D. Shames1, M. Kowanetz1, Y. Xiao2, Y. Choi3, M. D'Arcangelo4, C. Behrens5, L.M. Solis5, H. Koeppen6, R. Firestein7, Y. Wang1, S. Mocci8, T.A. Boyle4, M. Lund-Iversen9, C. Bowden8, L.C. Amler1, O.T. Brustugun10, I. Wistuba11, F.R. Hirsch12
  • 1Oncology Biomarker Development, Genentech, 94080 - South San Francisco/US
  • 2Biostatistics, Genentech Inc, 94080 - San Francisco/US
  • 3Biostatistics, Genentech, 94080 - South San Francisco/US
  • 4Cancer Center, Univeristy of Colorado, 80045 - Aurora/US
  • 5Thoracic/head And Neck Medical Oncology, M.D. Anderson, Houston/US
  • 6Pathology, Genentech, 94080 - South San Francisco/US
  • 7Pathology, Genentech, San Francisco/US
  • 8Pdo, Genentech, 94080 - South San Francisco/US
  • 9Pathology, Norwegian Radium Hospital, Oslo/NO
  • 10Oncology, Oslo University Hospital, Oslo/NO
  • 11Thoracic Head And Neck Medical Oncology, MD Anderson Cancer Center, Houston/US
  • 12Cancer Center, University of Colorado Denver, 80247 - Denver/US

Abstract

Aim

Novel molecularly targeted agents such as small molecule kinase inhibitors and antibodies targeted against immune check-point inhibitors have begun to erode the dominant position held by platinum-based chemotherapy in the treatment of NSCLC. While in some cases, activating kinase mutations appear to be mutually exclusive (EGFR and KRAS), there are many overlapping molecular subsets within NSCLC. As we continue to develop novel drugs, it is important that we develop a greater understanding of the prevalence, overlap, and prognostic significance of drug targets including activating mutations, signaling pathways, and tumor immune markers, as this will aid in trial design and predictive biomarker development for drug combinations or sequential treatment regimens.

Methods

Seven biomarkers - TTF1, p63, EGFR mutation, KRAS mutation, MET immunohistochemistry [IHC], PDL1 IHC, NaPI2B IHC- across two sample sets (Set 1, n = 561; Set 2, n = 310) were tested. Set 1 contained surgically resected cases obtained at MD Anderson Cancer Center (MDA) during 2003-2005. Samples from Set 2 were part of a collaboration between the University of Colorado Cancer Center (UofC), USA and The Norwegian Radium Hospital, and contained surgically-resected NSCLC tissues collected from 2006–2011.

Results

The prevalence, overlap, and prognostic significance of each biomarker were compared between the two cohorts. Most endpoints were consistent between the cohorts. However, significant differences in prevalence were observed within adenocarcinomas for MET (50% vs. 34%, MDA vs. UofC; p < 0.0001) and PDL1 (47% vs. 33%, MDA vs. UofC p < 0.0001). Some differences were observed for squamous cell carcinoma, primarily for EGFR IHC (36% vs. 15%, p < 0.0001; MDA vs. UofC p < 0.0001). In addition, >67% of patients in both cohorts were positive for more than one biomarker and >33% were positive for at least three biomarkers. Correlations with patient characteristics and outcomes will be described in further detail.

Conclusions

These data suggest that the biomarker landscape in NSCLC is complex with most patients having multiple targetable alterations. Thus, the treatment landscape for NSCLC will become increasingly complex as more experimental agents approach pivotal testing.

Disclosure

D. Shames, M. Kowanetz, Y. Xiao, Y. Choi, H. Koeppen, R. Firestein, Y. Wang, S. Mocci, C. Bowden and L.C. Amler all declare that: I am an employee of Genentech Inc. I own stock in Roche Holdings.

All other authors have declared no conflicts of interest.