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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

4347 - Management of leptomeningeal metastases in EGFR mutated non-small cell lung cancer: analysis of tyrosine kinase inhibitors sequence.

Date

20 Oct 2018

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

Presenters

Ronan Flippot

Citation

Annals of Oncology (2018) 29 (suppl_8): viii493-viii547. 10.1093/annonc/mdy292

Authors

R. Flippot1, E. Auclin2, P. Biondani3, E. Le Rhun4, J. Adam5, D. Planchard6, C. Caramella7, C. Le Pechoux8, L. Lacroix9, A. Gazzah10, L. Mezquita Pérez6, B. Besse11

Author affiliations

  • 1 Medical Oncology, Gustave Roussy, 94800 - Villejuif/FR
  • 2 Oncology, Hopital European George Pompidou, 75015 - Paris/FR
  • 3 Oncology, Hôpital Paul Brousse, 94800 - Villejuif/FR
  • 4 Neuro-oncology, Neurosurgery Department, Roger Salengro Hospital, 59037 - Lille/FR
  • 5 Pathology, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 6 Medical Oncology, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 7 Radiology, Gustave Roussy, 94800 - Villejuif/FR
  • 8 Radiation Therapy, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 9 Biology, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 10 Drug Development Department, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 11 Dept Of Cancer Medicine, Gustave Roussy Institut de Cancérologie, 94805 - Villejuif/FR
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Resources

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.

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