Impact of body surface area (BSA) on efficacy of gefitinib in patients with non-small cell lung cancer (NSCLC).

Abstract

e19167 Background: Drug dosing of chemotherapeutic agents has traditionally been based on an estimated BSA to reduce the pharmacokinetic inter-patient variability. However, the approved dose of gefitinib was fixed at 250 mg/body/day. Our preliminary retrospective study showed a potential association between BSA and progression-free survival (PFS) in the gefitinib monotherapy in advanced NSCLC [ASCO 2012, #2607]. Here, we investigated the influence of BSA on efficacy of gefitinib, using data from a prospective cohort of NSCLC patients receiving gefitinib. Methods: The subjects were 154 consecutive, EGFR-tyrosine kinase inhibitor (TKI)-naïve NSCLC patients who were to receive gefitinib monotherapy between 2007 and 2012. Baseline BSA was estimated by height and weight in each patient. The association between BSA and survival time was assessed using log-rank test and stepwise multivariate Cox proportional hazard model. Results: Median BSA of the subjects was 1.42 m2 (range: 0.98-1.95). At the cutoff level in BSA of 1.50 m2, overall survival (OS) and PFS in the large BSA group were not different from those in the small BSA group in the univariate analysis, which was also shown in multivariate analysis (hazard ratio: 1.12, 95% confidence interval: 0.66-1.92 and 1.67, 0.86-3.44, respectively). Among subjects with EGFR-mutant tumors (n=125; 81%), BSA had no association with OS, but patients with larger BSA had significantly worse PFS in the multivariate analysis (1.59, 1.01-2.51). The association of BSA with PFS was highly sensitive to increase or decrease in the cutoff level of BSA: BSA ≥ 1.45 m2 vs. <1.45 m2, [1.18, 0.80-1.75]; BSA ≥ 1.55 m2 vs. <1.55 m2, [1.75, 1.11-2.78]; BSA ≥ 1.60 m2 vs. <1.60 m2, [1.32, 0.82-2.11]. Conclusions: In this cohort, PFS was significantly associated with BSA in EGFR-mutant NSCLC when BSA level was cut off by around the median score. Our findings might suggest the need for further investigation of dose finding PK/PD study stratified by BSA level in gefitinib therapy in EGFR-mutant NSCLC.