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. 2012 Aug 15;18(16):4406-14.
doi: 10.1158/1078-0432.CCR-12-0357. Epub 2012 Jun 25.

The impact of initial gefitinib or erlotinib versus chemotherapy on central nervous system progression in advanced non-small cell lung cancer with EGFR mutations

Stephanie Heon  1 , Beow Y Yeap, Neal I Lindeman, Victoria A Joshi, Mohit Butaney, Gregory J Britt, Daniel B Costa, Michael S Rabin, David M Jackman, Bruce E Johnson
Affiliations

The impact of initial gefitinib or erlotinib versus chemotherapy on central nervous system progression in advanced non-small cell lung cancer with EGFR mutations

Stephanie Heon et al. Clin Cancer Res. .

Abstract

Purpose: This retrospective study was undertaken to investigate the impact of initial gefitinib or erlotinib (EGFR tyrosine kinase inhibitor, EGFR-TKI) versus chemotherapy on the risk of central nervous system (CNS) progression in advanced non-small cell lung cancer (NSCLC) with EGFR mutations.

Experimental design: Patients with stage IV or relapsed NSCLC with a sensitizing EGFR mutation initially treated with gefitinib, erlotinib, or chemotherapy were identified. The cumulative risk of CNS progression was calculated using death as a competing risk.

Results: One hundred and fifty-five patients were eligible (EGFR-TKI: 101, chemotherapy: 54). Twenty-four patients (24%) in the EGFR-TKI group and 12 patients (22%) in the chemotherapy group had brain metastases at the time of diagnosis of advanced NSCLC (P = 1.000); 32 of the 36 received CNS therapy before initiating systemic treatment. Thirty-three patients (33%) in the EGFR-TKI group and 26 patients (48%) in the chemotherapy group developed CNS progression after a median follow-up of 25 months. The 6-, 12-, and 24-month cumulative risk of CNS progression was 1%, 6%, and 21% in the EGFR-TKI group compared with corresponding rates of 7%, 19%, and 32% in the chemotherapy group (P = 0.026). The HR of CNS progression for upfront EGFR-TKI versus chemotherapy was 0.56 [95% confidence interval (CI), 0.34-0.94].

Conclusions: Our data show lower rates of CNS progression in EGFR-mutant advanced NSCLC patients initially treated with an EGFR-TKI compared with upfront chemotherapy. If validated, our results suggest that gefitinib and erlotinib may have a role in the chemoprevention of CNS metastases from NSCLC.

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Conflict of interest statement

Disclosure of Potential Conflicts of Interest

V.A. Joshi: employment (KEW Group); ownership interest (KEW Group). D.B. Costa: consultant/advisory board (Pfizer; AstraZeneca; Roche). M.S. Rabin: consultant/advisory board (Genentech). D.M. Jackman: consultant/advisory board (Foundation Medicine; Genentech). B.E. Johnson: ownership interest (KEW Group); consultant/advisory board (Genentech; Pfizer; Chugai; AstraZeneca); post marketing royalties for EGFR mutation testing. No potential conflicts of interest were disclosed by the other authors.

Figures

Figure 1
Figure 1
Cumulative incidence of CNS progression in (A) all eligible patients, (B) patients without prior CNS involvement, and (C) patients with prior CNS involvement.
Figure 2
Figure 2
Overall survival in all eligible patients. OS, overall survival.
See this image and copyright information in PMC

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