Abstract 4347
Background
Non-small cell lung carcinomas (NSCLC) with leptomeningeal metastases are associated with poor outcomes. Tyrosine kinase inhibitors (TKI) in EGFR-mutated (EGFRm) tumors might have substantial activity. Impact of TKI sequence on survival and clinical benefit is unknown.
Methods
Consecutive patients (pts) from 2 institutions with EGFRm NSCLC and LM were included. Retrospective collection of clinical, pathological and radiological data was performed. Overall survival (OS), Progression-free survival (PFS), clinical response rate (CRR) and disease control rate (DCR; stable disease > 2 months or clinical response) were assessed. Evaluation of TKI sequence and dose modifications in pts who had LM progression with first-line TKI was performed.
Results
Seventy pts were enrolled from Apr. 2003 to Feb. 2018. Median age was 54 [26-79], 73% were female and 85% non-smokers. Median time from initial diagnosis to LM onset was 17.5 months (m) [0-106], and pts received a median of 2 [1-7] prior therapies before LM onset. Median OS from LM onset was 7m [95% CI 6-9]. After LM diagnosis, pts received a median of 2 [1-6] lines of systemic therapy. Forty pts received 2nd-line TKI after LM progression under TKI, with a 2nd-line median PFS of 3m [95% CI 2-not reached], CRR 38%, DCR 73%. In pts who switched treatment at LM progression (N = 36), 21 switched from any TKI to erlotinib (“E”,53%), 10 maintained erlotinib with either dose increase or concurrent bevacizumab (“HD-E”, 22%), 2 switched from erlotinib to afatinib or gefitinib (“A/G”, 6%), and 4 with T790M mutation switched from any TKI to osimertinib (“O”, 11%). Pts with E had 6-months PFS of 41%, median OS of 6 months [95% CI 3-7], and DCR of 62%. Both pts with A/G had absolute OS < 2m. Pts with HD-E had a median OS of 3 months [2-6] and a DCR of 80%. In T790M-mutated pts, O provided a median OS of 10 months [6-10] and a DCR of 100%.
Conclusions
TKIs in LM from EGFRm NSCLC provide disease control in most pts. Switch from afatinib/gefitinib to erlotinib provided extended survival for patients who progressed with first-line TKI. A higher dose of erlotinib might rescue resistance to erlotinib in subsets of pts.
Clinical trial identification
Legal entity responsible for the study
Gustave Roussy.
Funding
Has not received any funding.
Editorial Acknowledgement
Disclosure
All 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