Skin rash as useful marker of erlotinib efficacy in NSCLC and its impact on clinical practice

被引:20
作者
Fiala, O. [1 ]
Pesek, M. [2 ]
Finek, J. [1 ]
Krejci, J. [3 ]
Ricar, J. [4 ]
Bortlicek, Z. [5 ]
Benesova, L. [6 ]
Minarik, M. [6 ]
机构
[1] Univ Hosp Plzen, Dept Radiotherapy & Oncol, Brno, Czech Republic
[2] Univ Hosp Plzen, Dept TB & Resp Dis, Brno, Czech Republic
[3] Univ Hosp Prague Bulovka, Dept Pneumol & Thorac Surg, Brno, Czech Republic
[4] Univ Hosp Plzen, Dept Dermatovenerol, Brno, Czech Republic
[5] Masaryk Univ, Inst Biostat & Anal, Brno, Czech Republic
[6] Genomac Res Inst, Ctr Appl Genom Solid Tumors CEGES, Prague, Czech Republic
关键词
erlotinib; NSCLC; rash; targeted traetment; skin toxicity; GROWTH-FACTOR-RECEPTOR; CELL LUNG-CANCER; KRAS MUTATIONS; EGFR MUTATIONS; GENE-MUTATIONS; PHASE-III; INHIBITORS; GEFITINIB; ADENOCARCINOMA; CHEMOTHERAPY;
D O I
10.4149/neo_2013_004
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Erlotinib is an epidermal growth factor receptor tyrosine kinase inhibitor used in treatment of advanced NSCLC. Patients harboring EGFR or KRAS mutations represent minority of all patients in caucasian population and there is no available predictor for a predominant group of patients harboring the wild-type EGFR and wild-type KRAS genes. Skin rash is the most frequent manifestation of cutaneous toxicity of erlotinib. Rash is associated with a good therapeutic response. We aimed at the evaluation of rash as a predictor of therapeutic effect of erlotinib in patients harboring the wild-type EGFR and KRAS wild-type genes and to assess its possible usage in a clinical practice. Totally 184 patients with advanced stage NSCLC (IIIB, IV) harboring the wild-type EGFR and wild-type KRAS genes were analysed. Comparison of ORR, PFS and OS according to the occurrence of rash was performed. In order to assess the impact of rash in clinical practice it was conducted landmark analysis of the group of patients whose rash was observed during first month of treatment (n=124). Patients in whom progression was observed during the first month of treatment were excluded from the landmark analysis. The comparison of ORR was performed using Fisher's exact test, visualization of survival was performed using Kaplan-Meier survival curves and the differences in survival were tested using the log-rank test. Median PFS in patients who were observed with rash during the treatment was 3.0 vs. 1.2 months in patients with no rash (p<0.001), median of OS in patients who were observed with rash during the treatment was 13.9 vs. 5.8 months in patients with no rash (p<0.001). ORR in patients who were observed with rash during the treatment was 17.4% vs. 3.3% in patients with no rash (p=0.001). Median of PFS after 1 month of treatment in patients who were observed with rash during the first month was 2.9 vs. 1.1 months in patients with no rash (p=0.027). Median of OS after 1 month of treatment in patients who were observed with rash during the first month was 13.8 vs. 9.9 months in patients with no rash (p=0.082). Rash is strongly associated with better survival and ORR in patients harboring wild-type EGFR and wild-type KRAS genes. Occurrence of rash during the first month of treatment is a useful predictor of better effect of erlotinib after one month of treatment. Patients who were not observed with rash during the first month of treatment are in high risk of progression. Optimization of the treatment of these patients can contribute restaging after two months of treatment, assessment of plasma levels of erlotinib and eventually attempt to dose escalation.
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页码:26 / 32
页数:7
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