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.
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.
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%.
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.
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All authors have declared no conflicts of interest.