Sarcopenia as a predictor of initial administration dose of afatinib in patients with advanced non-small cell lung
Xin Nie1, Ping Zhang2, Jia-Yin Gao3
1Palliative Care Center & Daycare Center, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China.
Background:
Sarcopenia has recently emerged as a new condition with increasing importance in lung cancer patients. The aim of this study was to investigate the influence of sarcopenia on tolerance and efficacy of afatinib.
Methods:
We retrospectively evaluated 35 patients with epidermal growth factor receptor (EGFR) mutant advanced non-small cell lung cancer (NSCLC) treated with first-line afatinib. Skeletal muscle area (SMA) was measured at the third lumbar vertebra using routine conducted computed tomography (CT) images for evaluation of disease burden. Sarcopenia was defined as skeletal muscle index (SMI = SMA/height2 ) ≤38.5 cm2 /m2 for women and ≤52.4 cm2 /m2 for men based on previous criteria. Fisher's exact tests, Kaplan-Meier method, and logistic regression modeling were used.
Results:
The median age at diagnosis was 65 years (range,39-84 years). A total of 24 (68.6%) patients were diagnosed with sarcopenia. The most frequent adverse events (AEs) related to afatinib were diarrhea (94.3%) followed by rash (77.1%) and paronychia (60%). Overall, 19 (54.3%) patients had dose reduction. Sarcopenic patients had a significantly higher rate of grade ≥ 2 diarrhea (75.0 vs. 27.3%, p = 0.011) and toxicity-related dose reduction (75.0 vs. 9.1%, p = 0.001). Multivariate analysis also showed that sarcopenia (odds ratio [OR] 51.7, 95% confidence interval [CI]: 2.4-1081.3, p = 0.01) was an independent risk factor for dose reduction of afatinib. The median progression-free survival (PFS) for afatinib was 12.0 months (95% CI: 10.6-13.4). Both dose reduction and sarcopenia did not affect therapeutic efficacy.
Conclusions:
Toxicity-related dose reduction is common with initiation of afatinib 40 mg/day. Sarcopenic patients might begin treatment with a low dose of afatinib according to tolerance.
