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Skin rash as useful marker of erlotinib efficacy in NSCLC and its impact on clinical practice
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Abstracts / Lung Cancer 77 (2012) S28–S43
EGFR mutations in patients with advanced NSCLC Fiala 1,∗ ,
Pesek 2 ,
Finek 1 ,
Bruha 2 ,
Ondrej Milos Jindrich Frantisek Zbynek Bortlicek 3 , Jana Krejci 4 , Lucie Benesova 5 , Marek Minarik 5 . 1 Department of Oncology and Radiotherapy, University Hospital in Pilsen, Czech Republic, 2 Department of Tuberculosis and Respiratory Diseases, University Hospital in Pilsen, Czech Republic, 3 Institute of Biostatistics and Analyses, Masaryk University, Brno, Czech Republic, 4 Department of Pneumology and Thoracic Surgery, University Hospital in Prague-Bulovka, Czech Republic, 5 Center for Applied Genomics of Solid Tumors, Genomac Research Institute, Prague, Czech Republic Background: Molecular targeted therapy based on tyrosine kinase inhibitors, directed at the epidermal growth factor receptor (EGFR) is one of the novel options for management of NSCLC. EGFR mutations, exon 19 deletions and exon 21 point mutations (L858) are good predictors of response to EGFR-TKI treatment. The aim of this study was to assess the incidence of EGFR mutations in a large cohort of caucasians with advanced NSCLC and subsequently evaluate their impact on the effect of EGFR-TKI treatment. Methods: 613 patients with advanced NSCLC were genetically tested. The effect of treatment was evaluated in 410 patients treated with EGFR-TKI. Survival was evaluated using Kaplan–Meier method and statistical comparison was performed using log-rank test. Results: EGFR mutations were detected in 73 (11.9%) patients. Exon 19 deletions were detected in 49 patients, exon 21 point mutations (L858) were detected in 22 patients, both mutation types were detected in 2 patients. It was demonstrated an increased incidence of EGFR mutations among patients with adenocarcinoma (14.9% vs. 7.8%, p = 0.008), women (20.2% vs. 7.1%, p < 0.001) and nonsmokers (29.9% vs. 7.0%, p < 0.001). Median PFS in patients harboring EGFR mutation was 7.2 vs. 2.0 months in patients harboring wild-type EGFR (p < 0.001), median OS in patients harboring EGFR mutation was 14.5 vs. 7.5 months in patients harboring wild-type EGFR (p = 0.019). Conclusion: The incidence of EGFR mutations in the studied population, their increased incidence among patients with adenocarcinoma, women, non-smokers correlated with data previously published. Results of the analysis of survival in patients treated with EGFR-TKI confirmed the high potential of EGFR mutations to predict the good effect of the EGFR-TKI treatment. Genetic testing in patients with NSCLC should be a standard part of diagnostic procedure. http://dx.doi.org/10.1016/j.lungcan.2012.05.054 Skin rash as useful marker of erlotinib efficacy in NSCLC and its impact on clinical practice Ondrej Fiala 1,∗ , Milos Pesek 2 , Jindrich Finek 1 , Jana Krejci 3 , Jan Ricar 4 , Zbynek Bortlicek 5 , Lucie Benesova 6 , Marek Minarik 6 . 1 Department of Oncology and Radiotherapy, University Hospital in Pilsen, Czech Republic, 2 Department of Tuberculosis and Respiratory Diseases, University Hospital in Pilsen, Czech Republic, 3 Department of Pneumology and Thoracic Surgery, University Hospital in Prague-Bulovka, Czech Republic, 4 Department of Dermatovenerology, University Hospital in Pilsen, Czech Republic, 5 Institute of Biostatistics and Analyses, Masaryk University, Brno, Czech Republic, 6 Center for Applied Genomics of Solid Tumors, Genomac Research Institute, Prague, Czech Republic Introduction: Erlotinib is an EGFR tyrosine kinase inhibitor used in treatment of NSCLC. There is no available predictor for a predominant group of patients harboring the wild-type EGFR and wild-type KRAS genes. Skin rash is associated with a good therapeutic effect. We aimed at the evaluation of rash as a predictor of therapeutic
effect of erlotinib in this group of patients and assessment of its possible usage in a clinical practice. Methods: 184 patients with advanced stage NSCLC harboring the wild-type EGFR and wild-type KRAS genes treated with erlotinib were analysed. Comparison of ORR, PFS and OS according to the occurrence of rash was performed. The impact of rash in clinical practice was studied in a landmark analysis of a group of patients whose rash was observed during the first month of the treatment. Results: Median PFS in patients with rash was 3.0 vs. 1.2 months in patients with no rash (p < 0.001), median OS was 13.9 vs. 5.8 months (p < 0.001) and ORR was 17.4% vs. 3.3% (p < 0.001). Median PFS after 1 month of treatment in patients with rash during the first month was 2.9 vs. 1.1 months in patients with no rash (p = 0.027), median OS after 1 month of treatment was 13.8 vs. 9.9 months (p = 0.082). Conclusion: Rash is associated with better treatment efficacy in patients harboring wild-type EGFR and wild-type KRAS genes. Occurrence of rash during the first month is a useful predictor of better further survival. Patients who were not observed with rash during the first month of treatment are at high risk of early progression. http://dx.doi.org/10.1016/j.lungcan.2012.05.055 The relevance of stable disease (SD) as a surrogate end-point in advanced non-small cell lung cancer (NSCLC) patients treated with erlotinib (E) as the second/third line F. Grossi 1,∗ , C. Sini 1 , G. Barletta 1 , E. Rijavec 1 , C. Genova 1 , G. Dal Bello 1 , P. Pronzato 1 , P. Venturino 2 , G. Pappagallo 3 . 1 National Institute for Cancer Research, Genova, Italy, 2 Roche, Italy, 3 Azienda ULSS 13, Mirano, VE, Italy Background: SD has often been viewed as a result with an uncertain clinical value. With the advent of E in advanced NSCLC, increasing numbers of patients (pts) achieve SD as a best response. A common observation in clinical practice is that a high proportion of patients receiving E have durable SD. The aim of this analysis was to compare the progression-free survival (PFS) and overall survival (OS) in pts with advanced NSCLC who achieved confirmed SD or complete/partial response (CR + PR) after second/third line treatment with E. Methods: Data from 684 Italian pts from the TRUST trial (Tiseo et al., Lung Cancer, 2008) were analyzed. E was administered orally at 150 mg per day and was continued until disease progression, development of unacceptable toxicity or patient’s refusal. We define confirmed SD (cSD) if the patients’ PFS was ≥5 months (response to E was evaluated per protocol every two months) and reconfirmed SD (rSD) if the patients’ PFS was ≥8 months. Results: Pts’ characteristics included the following: median age, 67 years (31–89); females/males = 219/465 pts (32%/68%); never/ former smokers = 191/493 pts (28%/72%); squamous/adeno/ BAC/large cell/NOS = 163/361/26/21/113 pts (24%/53%/4%/3%/16%); ECOG PS 0–1/2–3 = 557/127 pts (81%/19%). In 83 pts (12%), E was administered as the first-line therapy in pts who were unable to receive chemotherapy; 305 pts (45%) had received 1 prior line of chemotherapy, and 296 pts (43%) had received 2 prior lines of chemotherapy. A total of 428 pts were evaluable for a response: 44 pts (10%) exhibited CR + PR, 226 pts (53%) attained SD, which consisted of 139 pts (32%) with cSD and 83 pts (19%) with rSD. The median PFS estimates (with 95% CI) were 13.1 months (9.8–16.4) for CR + PR pts, 9.9 months (8.2–11.4) for cSD pts and 14 months (12–16) for rSD. The median OS estimates (with 95% CI) were 24.0 months (17–31) for CR + PR pts, 17.9 months (14.4–21.5) for cSD pts and 24.9 months (18.1–31.7) for rSD. Conclusions: Our findings are the first to demonstrate the relevance of achieving stable disease with E treatment. Pts obtaining
Abstracts / Lung Cancer 77 (2012) S28–S43
EGFR mutations in patients with advanced NSCLC Fiala 1,∗ ,
Pesek 2 ,
Finek 1 ,
Bruha 2 ,
Ondrej Milos Jindrich Frantisek Zbynek Bortlicek 3 , Jana Krejci 4 , Lucie Benesova 5 , Marek Minarik 5 . 1 Department of Oncology and Radiotherapy, University Hospital in Pilsen, Czech Republic, 2 Department of Tuberculosis and Respiratory Diseases, University Hospital in Pilsen, Czech Republic, 3 Institute of Biostatistics and Analyses, Masaryk University, Brno, Czech Republic, 4 Department of Pneumology and Thoracic Surgery, University Hospital in Prague-Bulovka, Czech Republic, 5 Center for Applied Genomics of Solid Tumors, Genomac Research Institute, Prague, Czech Republic Background: Molecular targeted therapy based on tyrosine kinase inhibitors, directed at the epidermal growth factor receptor (EGFR) is one of the novel options for management of NSCLC. EGFR mutations, exon 19 deletions and exon 21 point mutations (L858) are good predictors of response to EGFR-TKI treatment. The aim of this study was to assess the incidence of EGFR mutations in a large cohort of caucasians with advanced NSCLC and subsequently evaluate their impact on the effect of EGFR-TKI treatment. Methods: 613 patients with advanced NSCLC were genetically tested. The effect of treatment was evaluated in 410 patients treated with EGFR-TKI. Survival was evaluated using Kaplan–Meier method and statistical comparison was performed using log-rank test. Results: EGFR mutations were detected in 73 (11.9%) patients. Exon 19 deletions were detected in 49 patients, exon 21 point mutations (L858) were detected in 22 patients, both mutation types were detected in 2 patients. It was demonstrated an increased incidence of EGFR mutations among patients with adenocarcinoma (14.9% vs. 7.8%, p = 0.008), women (20.2% vs. 7.1%, p < 0.001) and nonsmokers (29.9% vs. 7.0%, p < 0.001). Median PFS in patients harboring EGFR mutation was 7.2 vs. 2.0 months in patients harboring wild-type EGFR (p < 0.001), median OS in patients harboring EGFR mutation was 14.5 vs. 7.5 months in patients harboring wild-type EGFR (p = 0.019). Conclusion: The incidence of EGFR mutations in the studied population, their increased incidence among patients with adenocarcinoma, women, non-smokers correlated with data previously published. Results of the analysis of survival in patients treated with EGFR-TKI confirmed the high potential of EGFR mutations to predict the good effect of the EGFR-TKI treatment. Genetic testing in patients with NSCLC should be a standard part of diagnostic procedure. http://dx.doi.org/10.1016/j.lungcan.2012.05.054 Skin rash as useful marker of erlotinib efficacy in NSCLC and its impact on clinical practice Ondrej Fiala 1,∗ , Milos Pesek 2 , Jindrich Finek 1 , Jana Krejci 3 , Jan Ricar 4 , Zbynek Bortlicek 5 , Lucie Benesova 6 , Marek Minarik 6 . 1 Department of Oncology and Radiotherapy, University Hospital in Pilsen, Czech Republic, 2 Department of Tuberculosis and Respiratory Diseases, University Hospital in Pilsen, Czech Republic, 3 Department of Pneumology and Thoracic Surgery, University Hospital in Prague-Bulovka, Czech Republic, 4 Department of Dermatovenerology, University Hospital in Pilsen, Czech Republic, 5 Institute of Biostatistics and Analyses, Masaryk University, Brno, Czech Republic, 6 Center for Applied Genomics of Solid Tumors, Genomac Research Institute, Prague, Czech Republic Introduction: Erlotinib is an EGFR tyrosine kinase inhibitor used in treatment of NSCLC. There is no available predictor for a predominant group of patients harboring the wild-type EGFR and wild-type KRAS genes. Skin rash is associated with a good therapeutic effect. We aimed at the evaluation of rash as a predictor of therapeutic
effect of erlotinib in this group of patients and assessment of its possible usage in a clinical practice. Methods: 184 patients with advanced stage NSCLC harboring the wild-type EGFR and wild-type KRAS genes treated with erlotinib were analysed. Comparison of ORR, PFS and OS according to the occurrence of rash was performed. The impact of rash in clinical practice was studied in a landmark analysis of a group of patients whose rash was observed during the first month of the treatment. Results: Median PFS in patients with rash was 3.0 vs. 1.2 months in patients with no rash (p < 0.001), median OS was 13.9 vs. 5.8 months (p < 0.001) and ORR was 17.4% vs. 3.3% (p < 0.001). Median PFS after 1 month of treatment in patients with rash during the first month was 2.9 vs. 1.1 months in patients with no rash (p = 0.027), median OS after 1 month of treatment was 13.8 vs. 9.9 months (p = 0.082). Conclusion: Rash is associated with better treatment efficacy in patients harboring wild-type EGFR and wild-type KRAS genes. Occurrence of rash during the first month is a useful predictor of better further survival. Patients who were not observed with rash during the first month of treatment are at high risk of early progression. http://dx.doi.org/10.1016/j.lungcan.2012.05.055 The relevance of stable disease (SD) as a surrogate end-point in advanced non-small cell lung cancer (NSCLC) patients treated with erlotinib (E) as the second/third line F. Grossi 1,∗ , C. Sini 1 , G. Barletta 1 , E. Rijavec 1 , C. Genova 1 , G. Dal Bello 1 , P. Pronzato 1 , P. Venturino 2 , G. Pappagallo 3 . 1 National Institute for Cancer Research, Genova, Italy, 2 Roche, Italy, 3 Azienda ULSS 13, Mirano, VE, Italy Background: SD has often been viewed as a result with an uncertain clinical value. With the advent of E in advanced NSCLC, increasing numbers of patients (pts) achieve SD as a best response. A common observation in clinical practice is that a high proportion of patients receiving E have durable SD. The aim of this analysis was to compare the progression-free survival (PFS) and overall survival (OS) in pts with advanced NSCLC who achieved confirmed SD or complete/partial response (CR + PR) after second/third line treatment with E. Methods: Data from 684 Italian pts from the TRUST trial (Tiseo et al., Lung Cancer, 2008) were analyzed. E was administered orally at 150 mg per day and was continued until disease progression, development of unacceptable toxicity or patient’s refusal. We define confirmed SD (cSD) if the patients’ PFS was ≥5 months (response to E was evaluated per protocol every two months) and reconfirmed SD (rSD) if the patients’ PFS was ≥8 months. Results: Pts’ characteristics included the following: median age, 67 years (31–89); females/males = 219/465 pts (32%/68%); never/ former smokers = 191/493 pts (28%/72%); squamous/adeno/ BAC/large cell/NOS = 163/361/26/21/113 pts (24%/53%/4%/3%/16%); ECOG PS 0–1/2–3 = 557/127 pts (81%/19%). In 83 pts (12%), E was administered as the first-line therapy in pts who were unable to receive chemotherapy; 305 pts (45%) had received 1 prior line of chemotherapy, and 296 pts (43%) had received 2 prior lines of chemotherapy. A total of 428 pts were evaluable for a response: 44 pts (10%) exhibited CR + PR, 226 pts (53%) attained SD, which consisted of 139 pts (32%) with cSD and 83 pts (19%) with rSD. The median PFS estimates (with 95% CI) were 13.1 months (9.8–16.4) for CR + PR pts, 9.9 months (8.2–11.4) for cSD pts and 14 months (12–16) for rSD. The median OS estimates (with 95% CI) were 24.0 months (17–31) for CR + PR pts, 17.9 months (14.4–21.5) for cSD pts and 24.9 months (18.1–31.7) for rSD. Conclusions: Our findings are the first to demonstrate the relevance of achieving stable disease with E treatment. Pts obtaining