Abstract 2070
Background
Non-small cell lung cancer (NSCLC) with activating EGFR mutations in exon 19 and 21 usually responds to EGFR tyrosine kinase inhibitors (TKI), but sometimes the responses can only be maintained for a few months. The underlying mechanisms of such short responses have not been fully elucidated.
Methods
The genomic profiles of sixteen short-term responders (SR) that had progression free survival (PFS) of less than 6 months on the first-generation EGFR TKI were interrogated, in comparison to twelve long-term responders (LR) that had more than 24 months of PFS. All patients were diagnosed with advanced lung adenocarcinoma and harbored EGFR 19del or L855R mutation before treatment. Paired tumor samples collected before treatment and after relapse (or at the last follow-up) were subjected to next-generation sequencing of 416 cancer-relevant genes.
Results
SR patients were significantly younger than LR patients (p < 0.001). 88% of SR patients have TP53 variations compared to 13% in LR patients (p < 0.001), and 37.5% SR patients carry EGFR amplification, which is much higher than LR patients (8%). In addition, 12 SR patients (75%) were identified with other potential primary resistance mechanisms in pre-treatment samples, including PTEN loss, BIM deletion polymorphism, amplifications of EGFR, ERBB2, MET, HRAS and AKT2. Comparatively, only 3 LR patients (25%) were detected with EGFR or AKT1 amplification that could possibly exert resistance.
Conclusions
The diversified pre-existing resistance mechanisms in SR patients revealed the complexity of defining treatment strategies even for EGFR sensitive mutations.
Clinical trial identification
Legal entity responsible for the study
Fan Yun.
Funding
Has not received any funding.
Editorial Acknowledgement
Disclosure
X. Tong, X. Wu, Y.W. Shao: Employee: Geneseeq Technology Inc. J. Yan: Employee: Nanjing Geneseeq Technology Inc. All other authors have declared no conflicts of interest.
Resources from the same session
4679 - Correlative analyses of serum biomarkers and efficacy outcomes in the randomized phase 2 trial of lenvatinib (LEN), everolimus (EVE), or LEN+EVE in patients with metastatic renal cell carcinoma
Presenter: Chung-Han Lee
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
5379 - End-to-end learning to predict survival in patients with gastric cancer using convolutional neural networks
Presenter: Armin Meier
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
5394 - Detection of Targetable Kinase Fusions in 7260 patients in an integrated Cancer System
Presenter: Ankur Parikh
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
5884 - Clinical and analytical validation of an FDA approved comprehensive genomic profiling (CGP) assay incorporating multiple companion diagnostics for targeted and immunotherapies
Presenter: Yali Li
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
5912 - SET overexpression promotes colorectal cancer progression and determines poor outcome in patients with localized disease.
Presenter: Blanca Torrejón
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
1168 - The functional MDM4 genetic variant in advanced lung adenocarcinoma patients treated with EGFR-TKIs
Presenter: Nasha Zhang
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
3071 - PD-L1 expression on pre-treatment circulating tumour cells, but not serum VEGF, is predictive of response to pembrolizumab in melanoma
Presenter: Muhammad Khattak
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
4062 - Olaparib plus paclitaxel sensitivity in biomarker subgroups of gastric cancer
Presenter: Yu-Zhen Liu
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
4801 - A diagnostic model for hepatitis B virus-related hepatocellular carcinoma in China: a large-scale, multi-center study
Presenter: Tian Yang
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
4874 - Dissecting Gastric Cancer biology and how and when to use immunotherapy
Presenter: Meghna Das Thakur
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract