Factors associated with early progression of non‐small‐cell lung cancer treated by epidermal growth factor receptor tyrosine‐kinase inhibitors

Abstract

Epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKI) are a therapeutic option as second-line therapy in non-small-cell lung carcinoma (NSCLC), regardless of the EGFR gene status. Identifying patients with early progression during EGFR-TKI treatment will help clinicians to choose the best regimen, TKI or chemotherapy. From a prospective database, all patients treated with gefitinib or erlotinib between 2001 and 2010 were retrospectively reviewed. Patients were classified into two groups according to their tumor response by RECIST after 45 days of treatment, progressive disease (PD) or controlled disease (CD). Two hundred and sixty-eight patients were treated with EGFR-TKI, among whom 239 were classified as PD (n = 75) and CD (n = 164). Median overall survival was 77 days (95% CI 61–109) for PD and 385 days (95% CI 267–481) for CD. Patients with PD were of younger age (P = 0.004) and more frequently current smokers (P = 0.001) had more frequently a performance status ≥2 (P = 0.012), a weight loss ≥10% (P = 0.025), a shorter time since diagnosis (P < 0.0001), a pathological classification as non-otherwise-specified NSCLC (P = 0.01), and the presence of abdominal metastases (P = 0.008). In multivariate analysis, abdominal metastases were the only factor associated with early progression (odds ratio (OR) 2.17, 95% CI [1.12–4.19]; P = 0.021). Wild-type EGFR versus mutated EGFR was associated with early progression. The presence of abdominal metastasis was independently associated with early progression in metastatic NSCLC receiving EGFR-TKI.

Pre-treatment Neutrophil-to-Lymphocyte Ratio significantly affects progression free survival in positive EGFR mutation advanced lung adenocarcinoma with EGFR-TKI treatment in Bali, Indonesia

“…Research by Rozensztajn et al in Paris showed that age affects PFS of patients. Older age had lower risk of progression by 4% with an OR of 0.96 (95% CI 0.93-0.98, p = 0.005) [16]. Another study by Tsai et al in Taiwan had different results from this study.…”

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

“…One study compared the characteristics of patients who experience early progression with patients whose disease was controlled after receiving erlotinib or gefitinib for at least 7 days, and the univariate analysis results showed that weight loss ≥10% was one of clinical factors associated with early progression 17 . This was the only study reported weight loss was associated with poorer outcome in patients treated with EGFR-TKI.…”

Erlotinib augmentation with dapsone for rash mitigation and increased anti-cancer effectiveness

“…Depending on dosing and study conditions, erlotinib rash can be seen in 75–90 % of treated patients, being severe in ~10 % (Tan and Chan 2009 ; Jia et al 2009 ; Rozensztajn et al 2014 ) This rash is usually treated with topical antibiotics, meticulous skin care, minocycline and topical steroids (Kiyohara et al 2013 ). Development of an erlotinib rash confers clear but minor overall survival advantage when treating various cancers (Stepanski et al 2013 ; Kaburagi et al 2013 ; Peereboom et al 2010 ; Kiyohara et al 2013 ; Aranda et al 2012 ; Petrelli et al 2012 ; Fiala et al 2013 ) with some indication that greater rash severity is correlated with slightly longer OS than lesser severity rashes (Kiyohara et al 2013 ; Rozensztajn et al 2014 ; Petrelli et al 2012 ) A statistically significant association exists between higher erlotinib levels and greater likelihood of rash (Tiseo et al 2014 ; Fukudo et al 2013 ).…”