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

Abstract

Purpose The aim of this study is to evaluate the impact of weight loss at presentation on treatment outcomes of first-line EGFR-tyrosine kinase inhibitors (EGFR-TKI) in EGFR-TKI sensitive mutant NSCLC patients.Methods We retrospectively analyzed the clinical outcomes of 75 consecutive advanced NSCLC patients with EGFR-TKI sensitive mutations (exon 19 deletion or exon 21 L858R) received first-line gefitinib or erlotinib therapy according to weight loss status at presentation in our single center.Results Of 75 EGFR-TKI sensitive mutant NSCLC patients, 49 (65.3%) patients had no weight loss and 26 (34.7%) had weight loss at presentation, the objective response rate (ORR) to EGFR-TKI treatment were similar between the two groups (79.6% vs. 76.9%, p = 0.533). Patients without weight loss at presentation had significantly longer median progression free survival (PFS) (12.4 months vs. 7.6 months; hazard ratio [HR] 0.356, 95% confidence interval [CI] 0.212-0.596, p < 0.001) and overall survival (OS) (28.5 months vs. 20.7 months; HR 0.408, 95% CI 0.215-0.776, p = 0.006) than those with weight loss at presentation; moreover, the stratified analysis by EGFR-TKI sensitive mutation types also found similar trend between these two groups except for OS in EGFR exon 21 L858R mutation patients. Multivariate analysis identified weight loss at presentation and EGFR-TKI sensitive mutation types were independent predictive factors for PFS and OS.Conclusions Weight loss at presentation had a detrimental impact on PFS and OS in EGFR-TKI sensitive mutant advanced NSCLC patients treated with first-line EGFR-TKI. It should be considered as an important factor in the treatment decision or designing of EGFR-TKI clinical trials.

Body Mass Index, Weight Loss, and Mortality Risk in Advanced-Stage Non-Small Cell Lung Cancer Patients: A Focus on EGFR Mutation

“…In recent research [32], weight loss during definitive radiotherapy was observed to result in a worse OS rate in patients with locally advanced NSCLC. Previous research found that a weight reduction at presentation had a negative influence on the survival outcomes in patients with EGFR-mutant advanced NSCLC that was treated with first-line EGFR-TKI [33]. Weight loss, independent of EGFR mutation status, was linked with a poor outcome in our research.…”

MiR‐873 inhibition enhances gefitinib resistance in non‐small cell lung cancer cells by targeting glioma‐associated oncogene homolog 1

“…Gefitinib, an EGFR-TKI, is the first targeted drug to treat advanced-stage NSCLC. [38][39][40] Our data showed that gefitinib reduces cell viability and proliferation in PC9 cells. Angiogenesis was also inhibited by gefitinib.…”

The real‐world clinical outcomes and treatment patterns of patients with unresectable locally advanced or metastatic soft tissue sarcoma treated with anlotinib in the post‐ALTER0203 trial era

“…Several retrospective studies reported that BMI and weight loss were associated with survival in patients with solid tumors who received TKI therapies. [21][22][23][24] However, changes in body weight may be masked by weight gain in ascites, peripheral edema, and growth of primary and metastatic tumors. 25,26 Therefore, in addition to sustained weight loss >5% or weight loss >2% with BMI <20 kg/m 2 , sarcopenia was also taken into consideration in the international consensus for cachexia diagnostic criteria.…”

“…Malnutrition is a severe problem affecting prognosis and quality of life in patients receiving anticancer therapy. Several retrospective studies reported that BMI and weight loss were associated with survival in patients with solid tumors who received TKI therapies 21–24 . However, changes in body weight may be masked by weight gain in ascites, peripheral edema, and growth of primary and metastatic tumors 25,26 .…”