1714P - KRAS in Non-Small Cell Lung Cancer

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Lung and other Thoracic Tumours
Pathology/Molecular Biology
Presenter Idoroenyi Amanam
Citation Annals of Oncology (2017) 28 (suppl_5): v595-v604. 10.1093/annonc/mdx391
Authors I. Amanam, R. Gupta, I. Mambetsariev, M. Koczywas, M. Cristea, E. Massarelli, K.L. Reckamp, R. Salgia
  • Medical Oncology And Therapeutics Research, City of Hope, 91010 - Duarte/US

Abstract

Background

Disease heterogeneity with variable molecular mutations is one of the main contributory factors in non-small cell lung cancer (NSCLC). The goal of this study was to better understand the KRAS patients with co-occurring mutations.

Methods

We identified 60 patients with a diagnosis of NSCLC and a KRAS mutation in the COH Cancer Registry from 2009 to 2016. Next generation sequencing was performed.

Results

Of the 60 patients identified, 42 (70%) were Stage IV at diagnosis, 7 (12%) Stage I and 7 (12%) stage II and 4 (6%) Stage III. 47% (78) patients were smokers. Caucasian was the most common 44 (73%) racial group, followed by Asians 9 (15%), African-Americans 3 (5%), other 3(5%) and Pacific Islander 1 (1.7%). The average age at diagnosis was 67 (median 69.5) years; 30 patients (50%) were > 70 years, 23 (38%) patients were 51-69 years, and 7 (12%) 50 years or less. The most common histology was adenocarcinoma 52 (87%), then adenosquamous 3 (5%), large cell 2 (3%) and small cell, squamous cell and carcinosarcoma (1 each, less than 2% each). Majority had metastatic disease 52 (87%) with 20% (12) metastasis to brain, with average 1.6 metastatic sites. An average of 1.97 (range = 0-5) lines of therapy including chemotherapy, biologic agents or immunotherapy were received. 12 (20%) patients received immunotherapy, radiation in 28 (47%) and surgery in 22 (37%) with a median overall survival at 15 months. The most frequent molecular alteration was codon 12 mutation (47, 78%), followed by codon 13 (7, 12%) and codon 61 (6, 10%) mutations. The most common co-occurring mutations in this cohort were TP53 (15, 25%), ATM (9, 15%), LRP1B (9, 15%), ARID1A (8, 13%), STK11 (8, 13%), ARID1B (7, 12%), TERT (7, 12%), EGFR (6, 10%), RBM10 (6, 10%), SPTA1 (6, 10%). We are currently evaluating the relevance of the Circos plot analysis for these mutations, clinical response to immunotherapy and potential biomarkers.

Conclusions

KRAS mutations are among the most common molecular alterations identified in NSCLC. The discovery of effective treatments targeting KRAS mutations has represented a challenge so far. Understanding the significance of co-mutations and their therapeutic implications, especially in response to immunotherapy agents represents an important step to develop better treatment options for KRAS mutated lung cancers.

Clinical trial identification

Legal entity responsible for the study

City of Hope National Medical Center

Funding

None

Disclosure

All authors have declared no conflicts of interest.