Abstract 1036
Background
MET exon 14 splice sites mutations define a unique subset of NSCLC patients who may benefit from MET inhibitors. Patterns of disease spread and response to chemotherapy in these patients are still poorly known.
Methods
Clinicopathologic characteristics and outcome of patients harboring MET exon 14 splice sites mutations identified in a single molecular center were retrospectively collected.
Results
We identified 39 patients from 12 french institutions between July 2009 and February 2018. Median age was 75 (range 55-91), sex ratio was 1.16 (M/W), 15 patients (38%) were never smokers. histologic type was adenocarcinoma in 31 tumors (79%) pulmonary sarcomatoid carcinoma in 3 tumors (8%) and NOS NSCLC in 5 tumors (13%). MET exon 14 alterations were deletions in 21 patients (54%), point mutations in 14 patients (36%) and delins in 4 patients (10%). Ten patients had a concurrent TP53 mutation, 3 patients had a RAS mutation, and 1 patient had a PIK3CA mutation. Among the 14 patients tested for PDL1 expression, 9 (64%) were PDL1 high (≥50%). The disease was diagnosed at stage IIIB/IV in 24 patients (62%) . Among those, the most frequent metastatic sites at diagnosis were bones (61%), lung (43%), pleura (39%) and brain (13%). 17 patients received at least one line of chemotherapy. Objective response rate for 1st line chemotherapy was 44%. Anti-PD1 agent was initiated in 6 patients, 1 patient (16%) achieved an objective response. MET TKI was initiated in 7 patients. Median overall survival for stage IIIB/IV patients was 8.5 months.
Conclusions
NSCLC patients harboring a MET exon 14 splice sites mutation are characterized by older age, never smoking status in half of the cases, and metastatic spread to bones. Future efforts should focus on identifying predictive markers of response to MET TKIs.
Clinical trial identification
Legal entity responsible for the study
Alexis Cortot.
Funding
Has not received any funding.
Editorial Acknowledgement
Disclosure
P. Jamme: Travel, Accommodations, Expenses: Chugai Pharma; Consulting: Boehringer Ingelheim International. C. Descarpentries: Personal fees: Roche, AstraZeneca and Boehringer. E. Dansin: Honoraria: BMS, MSD, AstraZeneca, Lilly and Roche (research support 2014). S. Baldacci: Personal fees: Lilly, GSK, Pfizer, Roche for activities outside the written work. A. Cortot: Travel, Accommodations, Expenses: AstraZeneca, Pfizer, Roche; Consulting for Boehringer Ingelheim International, Pfizer, Roche, MSD, AstraZeneca; Honoraria: Takeda, BMS; Research funding: Merck, Novartis. All other authors have declared no conflicts of interest.
Resources from the same session
5877 - TCR beta chain convergence defines the tumor infiltrating T cell repertoire of melanoma and non-small cell lung carcinoma.
Presenter: Timothy Looney
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
3212 - PI3K inhibition and modulation of immune and tumor microenvironment markers by copanlisib in patients with non-Hodgkin's lymphoma or advanced solid tumors
Presenter: Ahmad Awada
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
3574 - Pan-squamous genomic profiling stratified by anatomic tumor site and viral association
Presenter: Meagan Montesion
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
4113 - Toward the Standardization of Bioinformatics Methods for the Accurate Assessment of Tumor Mutational Burden (TMB)
Presenter: Han Chang
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
4468 - Prediction of primary resistance to anti-PD1 therapy (APD1) in 2nd line NSCLC
Presenter: Egbert Smit
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
4570 - Immunomodulatory germline variation impacts the development of multiple primary melanoma (MPM).
Presenter: Robert Ferguson
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
1169 - Leukocyte telomere length and recurrence risk after EGFR-TKIs therapy in patients with advanced lung adenocarcinoma
Presenter: Ming 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
1707 - Gene embedding: a novel machine learning approach to identify gene candidates related to immunotherapy responsiveness
Presenter: Chi Tung Choy
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
2123 - Common and rare DPYD variants are predictive for 5FU/capecitabine (5FU) toxicity: The MRC COIN and COIN-B trials
Presenter: Ayman Madi
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
5671 - The landscape of NTRK fusions in Chinese solid tumor patients
Presenter: Qi Ling
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