Evaluation of gefitinib efficacy according to body mass index, body surface area, and body weight in patients with EGFR-mutated advanced non-small cell lung cancer

Abstract

PurposeIn patients with epidermal growth factor receptor (EGFR)-mutated, advanced, non-small cell lung cancer (NSCLC), common gefitinib-sensitive EGFR mutations that predict a greater response to therapy include the exon 19 deletion and L858R point mutation. The objective of this study was to evaluate whether body surface area (BSA), body weight (BW), and body mass index (BMI) affect gefitinib efficacy in such patients.MethodsThe medical charts of 138 consecutive patients with advanced NSCLC harboring sensitive EGFR mutations, who underwent gefitinib treatment, were reviewed. The median BSA and BW were used as cutoff values to evaluate their impact on gefitinib efficacy. BMI was categorized as underweight (<18.5 kg/m2), normal (18.5–25 kg/m2), and overweight (≥25 kg/m2).ResultsThe median BSA and BW were 1.48 m2 and 53 kg, respectively. The overall response rate, progression-free survival (PFS), and overall survival (OS) were 65.2%, 12.2, and 24.2 months, respectively. There were no significant differences in clinical outcomes according to BSA, BW, or BMI alone. Subgroup analysis based on the mutation type and BSA revealed no significant differences in PFS between the groups; however, the median OS in those with exon 19 deletion combined with low BSA was significantly favorable compared with the other groups.ConclusionsGefitinib efficacy in patients with NSCLC harboring sensitive EGFR mutations did not differ according to BSA, BW, and BMI. However, OS was superior in patients with both the exon 19 deletion and low BSA.Electronic supplementary materialThe online version of this article (doi:10.1007/s00280-016-3232-2) contains supplementary material, which is available to authorized users.

Population pharmacokinetics of afatinib and exposure-safety relationships in Japanese patients with EGFR mutation-positive non-small cell lung cancer

“…reported that gefitinib efficacy in patients with EGFR-mutated advanced NSCLC did not differ according to BSA, body weight, or BMI. However, OS was higher in patients with both exon 19 deletion and low BSA than in patients without these characteristics 18 . These results suggested that BSA- and body weight-based dose adjustments could affect the treatment with EGFR TKIs.…”

Low Body Mass Index Is an Independent Prognostic Factor in Patients With Non-Small Cell Lung Cancer Treated With Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor

“…Underweight (BMI < 18.5 kg/m 2 ) has been shown as a worse prognostic factor not only in operable patients with early stage of lung cancer [20-22], but also in patients with advanced lung cancer [2, 23]. In contrast, regarding patients with mutant EGFR, BMI has been controversial as a prognostic factor [24-27]. Two Japanese studies of 138 patients treated with gefitinib [24] and of 47 patients with acquired T790M-positive mutation who had been treated with osimertinib after prior EGFR-TKI [25] failed to show any significant differences in response and PFS among underweight, normal weight and overweight patients, and between patients with BMI < 21.5 and those with BMI ≥ 21.5, respectively.…”

“…In contrast, regarding patients with mutant EGFR, BMI has been controversial as a prognostic factor [24-27]. Two Japanese studies of 138 patients treated with gefitinib [24] and of 47 patients with acquired T790M-positive mutation who had been treated with osimertinib after prior EGFR-TKI [25] failed to show any significant differences in response and PFS among underweight, normal weight and overweight patients, and between patients with BMI < 21.5 and those with BMI ≥ 21.5, respectively. Oppositely, in a Korean study of 95 patients, patients with BMI ≤ 20.8 had a longer PFS than those with BMI > 20.8 [27].…”

Impact of Weight Loss at Presentation on Survival in Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKI) Sensitive Mutant Advanced Non-small Cell Lung Cancer (NSCLC) Treated with First-line EGFR-TKI

“…Interestingly, several studies investigated the impact of other weight-related clinical characteristics such as body mass index (BMI), body surface area (BSA), and body weight (BW) at diagnosis on survival for EGFR-TKI therapy in EGFR mutant NSCLC patients 18 - 21 . However, the conclusions of these studies about the effects of BMI and BSA on survival were controversial and no predictive value of BW on the efficacy of EGFR-TKI was found.…”