Beyond disease-progression: Clinical outcomes after EGFR-TKIs in a cohort of EGFR mutated NSCLC patients

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Abstract

© 2017 Tudor et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Purpose: Treatment and clinical-outcomes were described in a sub-cohort of non-small-cell lung cancer (NSCLC) patients with disease-progression (PD) after epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs) treatment. Patients and methods: We retrospectively analyzed a single-institutional EGFR mutation positive (EGFRmut + ) NSCLC cohort for post-TKI-PD management, and assessed overall survival (OS) and post-progression survival (PPS). All de-novo (first lung-cancer occurrence) stage IIIA-IV patients, as well as de-novo stage IV subset was analyzed. Multi-state modeling (MSM) and a Cox PH regression model with propensity score weights adjusted for clinicopathological variables between: diagnosis and PD and PD to death. Results: 123 stage IIIA-IV patients were identified with 104 meeting RECIST-1.1-PD criteria. This RECIST-1.1-PD criteria subset included females (64.6%), Asians (39.4%), never/non-smokers (55.8%), and exon 19 deletion carriers (44.2%). Commonest treatment beyond initial-PD was continuing TKI alone (46/104), with another 21 patients continuing TKI plus additional systemic therapy. The median OS for patients who continued TKI treatment at initial-PD was 21.1 months versus 15.6 months for patients who discontinued TKI, p = 0.006. Via MSM analysis, continuing TKI at initial-PD followed by other systemic therapy was associated with an 83% reduced death risk, adjusted HR: 0.17 (95% CI: 0.07, 0.39). In the Cox PH model, ever-smokers with an exon 19 deletion had increased risk of death after PD (adjusted HR: 3.19, 95% CI: 1.54, 6.58), as did exon 21 mutation carriers, (adjusted HR: 2.10, 95% CI: 1.10, 4.00) and females (adjusted HR: 3.19, 95% CI: 1.54, 6.58). Conclusion: Subsequent systemic therapy after continuing TKI at initial-PD reduced the risk of death. Additionally, our data suggest that positive smoking history increases death risk for some EGFR mutation types and females.

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Tudor, R. A., D’Silva, A., Tremblay, A., MacEachern, P., Morris, D., Brenner, D., … Bebb, D. G. (2017). Beyond disease-progression: Clinical outcomes after EGFR-TKIs in a cohort of EGFR mutated NSCLC patients. PLoS ONE, 12(8). https://doi.org/10.1371/journal.pone.0181867

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