Impact of body surface area on survival in EGFR-mutant non-small cell lung cancer patients treated with gefitinib monotherapy: observational study of the Okayama Lung Cancer Study Group 0703

Abstract Background: The approved dose of gefitinib is fixed, without adjustment for physical size. We demonstrated previously that its efficacy was affected by body surface area (BSA) in patients with EGFR-mutant non-small cell lung cancer (NSCLC). To validate these observations, we assessed the association between BSA and the efficacy of gefitinib using a different patient cohort. Methods: Prospective cohort data from 115 NSCLC patients with EGFR-mutant tumours, who received gefitinib monotherapy between 2007 and 2012, were analysed. Results: Gefitinib was less effective in individuals with a high BSA (≥1.5 m²) in EGFR-mutant NSCLC compared with those with a low BSA (<1.5 m²). The median progression-free survival (PFS) in the high- and low-BSA groups was 4.2 and 8.5 months, respectively, although there was no difference in survival among the whole NSCLC cohort. Multivariate analysis also showed a significant effect of BSA on PFS (hazard ratio 1.72; 95 % confidence interval 1.08-2.74; p = 0.021). Sensitivity analysis revealed that the use of the BSA cut-off level around 1.50 m² was robust for detecting subpopulations that would benefit less from gefitinib monotherapy. Conclusion: We found in the prospective cohort data that BSA could affect the efficacy of gefitinib monotherapy in patients with EGFR-mutant NSCLC, suggesting that BSA-based dose setting of gefitinib monotherapy might be further investigated, despite the fact that no molecular-targeted agent described to date undergoes dose adjustment according to BSA.