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Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial

Summary Background There is a major unmet need for effective treatments in patients with squamous cell carcinoma of the lung. LUX-Lung 8 compared afatinib (an irreversible ErbB family blocker) with erlotinib (a reversible EGFR tyrosine kinase inhibitor), as second-line treatment for patients with ad... Full description

Journal Title: The lancet oncology 2015, Vol.16 (8), p.897-907
Main Author: Soria, Jean-Charles, Prof
Other Authors: Felip, Enriqueta, MD , Cobo, Manuel, MD , Lu, Shun, MD , Syrigos, Konstantinos, Prof , Lee, Ki Hyeong, MD , Göker, Erdem, MD , Georgoulias, Vassilis, Prof , Li, Wei, MD , Isla, Dolores, MD , Guclu, Salih Z, MD , Morabito, Alessandro, MD , Min, Young J, MD , Ardizzoni, Andrea, MD , Gadgeel, Shirish M, Prof , Wang, Bushi, PhD , Chand, Vikram K, MD , Goss, Glenwood D, Prof
Format: Electronic Article Electronic Article
Language: English
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Quelle: Alma/SFX Local Collection
Publisher: England: Elsevier Ltd
ID: ISSN: 1470-2045
Link: https://www.ncbi.nlm.nih.gov/pubmed/26156651
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title: Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial
format: Article
creator:
  • Soria, Jean-Charles, Prof
  • Felip, Enriqueta, MD
  • Cobo, Manuel, MD
  • Lu, Shun, MD
  • Syrigos, Konstantinos, Prof
  • Lee, Ki Hyeong, MD
  • Göker, Erdem, MD
  • Georgoulias, Vassilis, Prof
  • Li, Wei, MD
  • Isla, Dolores, MD
  • Guclu, Salih Z, MD
  • Morabito, Alessandro, MD
  • Min, Young J, MD
  • Ardizzoni, Andrea, MD
  • Gadgeel, Shirish M, Prof
  • Wang, Bushi, PhD
  • Chand, Vikram K, MD
  • Goss, Glenwood D, Prof
subjects:
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents - adverse effects
  • Antineoplastic Agents - therapeutic use
  • Carcinoma, Squamous Cell - drug therapy
  • Carcinoma, Squamous Cell - enzymology
  • Carcinoma, Squamous Cell - mortality
  • Carcinoma, Squamous Cell - pathology
  • Care and treatment
  • Cervical cancer
  • College teachers
  • Disease Progression
  • Disease-Free Survival
  • Erlotinib
  • FDA approval
  • Female
  • Hematology, Oncology and Palliative Medicine
  • Humans
  • Intention to Treat Analysis
  • Kaplan-Meier Estimate
  • Lung cancer
  • Lung Neoplasms - drug therapy
  • Lung Neoplasms - enzymology
  • Lung Neoplasms - mortality
  • Lung Neoplasms - pathology
  • Male
  • Medical colleges
  • Middle Aged
  • Mutation
  • Neoplasm Staging
  • Oncology
  • Pharmaceutical industry
  • Product development
  • Protein Kinase Inhibitors - adverse effects
  • Protein Kinase Inhibitors - therapeutic use
  • Quinazolines - adverse effects
  • Quinazolines - therapeutic use
  • Receptor, Epidermal Growth Factor - antagonists & inhibitors
  • Receptor, Epidermal Growth Factor - metabolism
  • Squamous cell carcinoma
  • Time Factors
  • Treatment Outcome
  • Tumor Burden
ispartof: The lancet oncology, 2015, Vol.16 (8), p.897-907
description: Summary Background There is a major unmet need for effective treatments in patients with squamous cell carcinoma of the lung. LUX-Lung 8 compared afatinib (an irreversible ErbB family blocker) with erlotinib (a reversible EGFR tyrosine kinase inhibitor), as second-line treatment for patients with advanced squamous cell carcinoma of the lung. Methods We did this open-label, phase 3 randomised controlled trial at 183 cancer centres in 23 countries worldwide. We enrolled adults with stage IIIB or IV squamous cell carcinoma of the lung who had progressed after at least four cycles of platinum-based-chemotherapy. Participants were randomly assigned (1:1) to receive afatinib (40 mg per day) or erlotinib (150 mg per day) until disease progression. The randomisation was done centrally with an interactive voice or web-based response system and stratified by ethnic origin (eastern Asian vs non-eastern Asian). Clinicians and patients were not masked to treatment allocation. The primary endpoint was progression-free survival assessed by independent central review (intention-to-treat population). The key secondary endpoint was overall survival. This trial is registered with ClinicalTrials.gov , NCT01523587. Findings 795 eligible patients were randomly assigned (398 to afatinib, 397 to erlotinib). Median follow-up at the time of the primary analysis of progression-free survival was 6·7 months (IQR 3·1–10·2), at which point enrolment was not complete. Progression free-survival at the primary analysis was significantly longer with afatinib than with erlotinib (median 2·4 months [95% CI 1·9–2·9] vs 1·9 months [1·9–2·2]; hazard ratio [HR] 0·82 [95% CI 0·68–1·00], p=0·0427). At the time of the primary analysis of overall survival (median follow-up 18·4 months [IQR 13·8–22·4]), overall survival was significantly greater in the afatinib group than in the erloinib group (median 7·9 months [95% CI 7·2–8·7] vs 6·8 months [5·9–7·8]; HR 0·81 [95% CI 0·69–0·95], p=0·0077), as were progression-free survival (median 2·6 months [95% CI 2·0–2·9] vs 1·9 months [1·9–2·1]; HR 0·81 [95% CI 0·69–0·96], p=0·0103) and disease control (201 [51%] of 398 patients vs 157 [40%] of 397; p=0·0020). The proportion of patients with an objective response did not differ significantly between groups (22 [6%] vs 11 [3%]; p=0·0551). Tumour shrinkage occurred in 103 (26%) of 398 patients versus 90 (23%) of 397 patients. Adverse event profiles were similar in each group: 224 (57%) of 392 patients in the afati
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 1470-2045
fulltext: fulltext
issn:
  • 1470-2045
  • 1474-5488
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titleAfatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial
sourceAlma/SFX Local Collection
creatorSoria, Jean-Charles, Prof ; Felip, Enriqueta, MD ; Cobo, Manuel, MD ; Lu, Shun, MD ; Syrigos, Konstantinos, Prof ; Lee, Ki Hyeong, MD ; Göker, Erdem, MD ; Georgoulias, Vassilis, Prof ; Li, Wei, MD ; Isla, Dolores, MD ; Guclu, Salih Z, MD ; Morabito, Alessandro, MD ; Min, Young J, MD ; Ardizzoni, Andrea, MD ; Gadgeel, Shirish M, Prof ; Wang, Bushi, PhD ; Chand, Vikram K, MD ; Goss, Glenwood D, Prof
creatorcontribSoria, Jean-Charles, Prof ; Felip, Enriqueta, MD ; Cobo, Manuel, MD ; Lu, Shun, MD ; Syrigos, Konstantinos, Prof ; Lee, Ki Hyeong, MD ; Göker, Erdem, MD ; Georgoulias, Vassilis, Prof ; Li, Wei, MD ; Isla, Dolores, MD ; Guclu, Salih Z, MD ; Morabito, Alessandro, MD ; Min, Young J, MD ; Ardizzoni, Andrea, MD ; Gadgeel, Shirish M, Prof ; Wang, Bushi, PhD ; Chand, Vikram K, MD ; Goss, Glenwood D, Prof ; LUX-Lung 8 Investigators
descriptionSummary Background There is a major unmet need for effective treatments in patients with squamous cell carcinoma of the lung. LUX-Lung 8 compared afatinib (an irreversible ErbB family blocker) with erlotinib (a reversible EGFR tyrosine kinase inhibitor), as second-line treatment for patients with advanced squamous cell carcinoma of the lung. Methods We did this open-label, phase 3 randomised controlled trial at 183 cancer centres in 23 countries worldwide. We enrolled adults with stage IIIB or IV squamous cell carcinoma of the lung who had progressed after at least four cycles of platinum-based-chemotherapy. Participants were randomly assigned (1:1) to receive afatinib (40 mg per day) or erlotinib (150 mg per day) until disease progression. The randomisation was done centrally with an interactive voice or web-based response system and stratified by ethnic origin (eastern Asian vs non-eastern Asian). Clinicians and patients were not masked to treatment allocation. The primary endpoint was progression-free survival assessed by independent central review (intention-to-treat population). The key secondary endpoint was overall survival. This trial is registered with ClinicalTrials.gov , NCT01523587. Findings 795 eligible patients were randomly assigned (398 to afatinib, 397 to erlotinib). Median follow-up at the time of the primary analysis of progression-free survival was 6·7 months (IQR 3·1–10·2), at which point enrolment was not complete. Progression free-survival at the primary analysis was significantly longer with afatinib than with erlotinib (median 2·4 months [95% CI 1·9–2·9] vs 1·9 months [1·9–2·2]; hazard ratio [HR] 0·82 [95% CI 0·68–1·00], p=0·0427). At the time of the primary analysis of overall survival (median follow-up 18·4 months [IQR 13·8–22·4]), overall survival was significantly greater in the afatinib group than in the erloinib group (median 7·9 months [95% CI 7·2–8·7] vs 6·8 months [5·9–7·8]; HR 0·81 [95% CI 0·69–0·95], p=0·0077), as were progression-free survival (median 2·6 months [95% CI 2·0–2·9] vs 1·9 months [1·9–2·1]; HR 0·81 [95% CI 0·69–0·96], p=0·0103) and disease control (201 [51%] of 398 patients vs 157 [40%] of 397; p=0·0020). The proportion of patients with an objective response did not differ significantly between groups (22 [6%] vs 11 [3%]; p=0·0551). Tumour shrinkage occurred in 103 (26%) of 398 patients versus 90 (23%) of 397 patients. Adverse event profiles were similar in each group: 224 (57%) of 392 patients in the afatinib group versus 227 (57%) of 395 in the erlotinib group had grade 3 or higher adverse events. We recorded higher incidences of treatment-related grade 3 diarrhoea with afatinib (39 [10%] vs nine [2%]), of grade 3 stomatitis with afatinib (16 [4%] vs none), and of grade 3 rash or acne with erlotinib (23 [6%] vs 41 [10%]). Interpretation The significant improvements in progression-free survival and overall survival with afatinib compared with erlotinib, along with a manageable safety profile and the convenience of oral administration suggest that afatinib could be an additional option for the treatment of patients with squamous cell carcinoma of the lung. Funding Boehringer Ingelheim.
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languageeng
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subjectAdult ; Aged ; Aged, 80 and over ; Antineoplastic Agents - adverse effects ; Antineoplastic Agents - therapeutic use ; Carcinoma, Squamous Cell - drug therapy ; Carcinoma, Squamous Cell - enzymology ; Carcinoma, Squamous Cell - mortality ; Carcinoma, Squamous Cell - pathology ; Care and treatment ; Cervical cancer ; College teachers ; Disease Progression ; Disease-Free Survival ; Erlotinib ; FDA approval ; Female ; Hematology, Oncology and Palliative Medicine ; Humans ; Intention to Treat Analysis ; Kaplan-Meier Estimate ; Lung cancer ; Lung Neoplasms - drug therapy ; Lung Neoplasms - enzymology ; Lung Neoplasms - mortality ; Lung Neoplasms - pathology ; Male ; Medical colleges ; Middle Aged ; Mutation ; Neoplasm Staging ; Oncology ; Pharmaceutical industry ; Product development ; Protein Kinase Inhibitors - adverse effects ; Protein Kinase Inhibitors - therapeutic use ; Quinazolines - adverse effects ; Quinazolines - therapeutic use ; Receptor, Epidermal Growth Factor - antagonists & inhibitors ; Receptor, Epidermal Growth Factor - metabolism ; Squamous cell carcinoma ; Time Factors ; Treatment Outcome ; Tumor Burden
ispartofThe lancet oncology, 2015, Vol.16 (8), p.897-907
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1Felip, Enriqueta, MD
2Cobo, Manuel, MD
3Lu, Shun, MD
4Syrigos, Konstantinos, Prof
5Lee, Ki Hyeong, MD
6Göker, Erdem, MD
7Georgoulias, Vassilis, Prof
8Li, Wei, MD
9Isla, Dolores, MD
10Guclu, Salih Z, MD
11Morabito, Alessandro, MD
12Min, Young J, MD
13Ardizzoni, Andrea, MD
14Gadgeel, Shirish M, Prof
15Wang, Bushi, PhD
16Chand, Vikram K, MD
17Goss, Glenwood D, Prof
18LUX-Lung 8 Investigators
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0Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial
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addtitleLancet Oncol
descriptionSummary Background There is a major unmet need for effective treatments in patients with squamous cell carcinoma of the lung. LUX-Lung 8 compared afatinib (an irreversible ErbB family blocker) with erlotinib (a reversible EGFR tyrosine kinase inhibitor), as second-line treatment for patients with advanced squamous cell carcinoma of the lung. Methods We did this open-label, phase 3 randomised controlled trial at 183 cancer centres in 23 countries worldwide. We enrolled adults with stage IIIB or IV squamous cell carcinoma of the lung who had progressed after at least four cycles of platinum-based-chemotherapy. Participants were randomly assigned (1:1) to receive afatinib (40 mg per day) or erlotinib (150 mg per day) until disease progression. The randomisation was done centrally with an interactive voice or web-based response system and stratified by ethnic origin (eastern Asian vs non-eastern Asian). Clinicians and patients were not masked to treatment allocation. The primary endpoint was progression-free survival assessed by independent central review (intention-to-treat population). The key secondary endpoint was overall survival. This trial is registered with ClinicalTrials.gov , NCT01523587. Findings 795 eligible patients were randomly assigned (398 to afatinib, 397 to erlotinib). Median follow-up at the time of the primary analysis of progression-free survival was 6·7 months (IQR 3·1–10·2), at which point enrolment was not complete. Progression free-survival at the primary analysis was significantly longer with afatinib than with erlotinib (median 2·4 months [95% CI 1·9–2·9] vs 1·9 months [1·9–2·2]; hazard ratio [HR] 0·82 [95% CI 0·68–1·00], p=0·0427). At the time of the primary analysis of overall survival (median follow-up 18·4 months [IQR 13·8–22·4]), overall survival was significantly greater in the afatinib group than in the erloinib group (median 7·9 months [95% CI 7·2–8·7] vs 6·8 months [5·9–7·8]; HR 0·81 [95% CI 0·69–0·95], p=0·0077), as were progression-free survival (median 2·6 months [95% CI 2·0–2·9] vs 1·9 months [1·9–2·1]; HR 0·81 [95% CI 0·69–0·96], p=0·0103) and disease control (201 [51%] of 398 patients vs 157 [40%] of 397; p=0·0020). The proportion of patients with an objective response did not differ significantly between groups (22 [6%] vs 11 [3%]; p=0·0551). Tumour shrinkage occurred in 103 (26%) of 398 patients versus 90 (23%) of 397 patients. Adverse event profiles were similar in each group: 224 (57%) of 392 patients in the afatinib group versus 227 (57%) of 395 in the erlotinib group had grade 3 or higher adverse events. We recorded higher incidences of treatment-related grade 3 diarrhoea with afatinib (39 [10%] vs nine [2%]), of grade 3 stomatitis with afatinib (16 [4%] vs none), and of grade 3 rash or acne with erlotinib (23 [6%] vs 41 [10%]). Interpretation The significant improvements in progression-free survival and overall survival with afatinib compared with erlotinib, along with a manageable safety profile and the convenience of oral administration suggest that afatinib could be an additional option for the treatment of patients with squamous cell carcinoma of the lung. Funding Boehringer Ingelheim.
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1Aged
2Aged, 80 and over
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4Antineoplastic Agents - therapeutic use
5Carcinoma, Squamous Cell - drug therapy
6Carcinoma, Squamous Cell - enzymology
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8Carcinoma, Squamous Cell - pathology
9Care and treatment
10Cervical cancer
11College teachers
12Disease Progression
13Disease-Free Survival
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15FDA approval
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17Hematology, Oncology and Palliative Medicine
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19Intention to Treat Analysis
20Kaplan-Meier Estimate
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22Lung Neoplasms - drug therapy
23Lung Neoplasms - enzymology
24Lung Neoplasms - mortality
25Lung Neoplasms - pathology
26Male
27Medical colleges
28Middle Aged
29Mutation
30Neoplasm Staging
31Oncology
32Pharmaceutical industry
33Product development
34Protein Kinase Inhibitors - adverse effects
35Protein Kinase Inhibitors - therapeutic use
36Quinazolines - adverse effects
37Quinazolines - therapeutic use
38Receptor, Epidermal Growth Factor - antagonists & inhibitors
39Receptor, Epidermal Growth Factor - metabolism
40Squamous cell carcinoma
41Time Factors
42Treatment Outcome
43Tumor Burden
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titleAfatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial
authorSoria, Jean-Charles, Prof ; Felip, Enriqueta, MD ; Cobo, Manuel, MD ; Lu, Shun, MD ; Syrigos, Konstantinos, Prof ; Lee, Ki Hyeong, MD ; Göker, Erdem, MD ; Georgoulias, Vassilis, Prof ; Li, Wei, MD ; Isla, Dolores, MD ; Guclu, Salih Z, MD ; Morabito, Alessandro, MD ; Min, Young J, MD ; Ardizzoni, Andrea, MD ; Gadgeel, Shirish M, Prof ; Wang, Bushi, PhD ; Chand, Vikram K, MD ; Goss, Glenwood D, Prof
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35Protein Kinase Inhibitors - therapeutic use
36Quinazolines - adverse effects
37Quinazolines - therapeutic use
38Receptor, Epidermal Growth Factor - antagonists & inhibitors
39Receptor, Epidermal Growth Factor - metabolism
40Squamous cell carcinoma
41Time Factors
42Treatment Outcome
43Tumor Burden
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16Chand, Vikram K, MD
17Goss, Glenwood D, Prof
aucorpLUX-Lung 8 Investigators
formatjournal
genrearticle
ristypeJOUR
atitleAfatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial
jtitleThe lancet oncology
addtitleLancet Oncol
date2015
risdate2015
volume16
issue8
spage897
epage907
pages897-907
issn1470-2045
eissn1474-5488
codenLANCAO
abstractSummary Background There is a major unmet need for effective treatments in patients with squamous cell carcinoma of the lung. LUX-Lung 8 compared afatinib (an irreversible ErbB family blocker) with erlotinib (a reversible EGFR tyrosine kinase inhibitor), as second-line treatment for patients with advanced squamous cell carcinoma of the lung. Methods We did this open-label, phase 3 randomised controlled trial at 183 cancer centres in 23 countries worldwide. We enrolled adults with stage IIIB or IV squamous cell carcinoma of the lung who had progressed after at least four cycles of platinum-based-chemotherapy. Participants were randomly assigned (1:1) to receive afatinib (40 mg per day) or erlotinib (150 mg per day) until disease progression. The randomisation was done centrally with an interactive voice or web-based response system and stratified by ethnic origin (eastern Asian vs non-eastern Asian). Clinicians and patients were not masked to treatment allocation. The primary endpoint was progression-free survival assessed by independent central review (intention-to-treat population). The key secondary endpoint was overall survival. This trial is registered with ClinicalTrials.gov , NCT01523587. Findings 795 eligible patients were randomly assigned (398 to afatinib, 397 to erlotinib). Median follow-up at the time of the primary analysis of progression-free survival was 6·7 months (IQR 3·1–10·2), at which point enrolment was not complete. Progression free-survival at the primary analysis was significantly longer with afatinib than with erlotinib (median 2·4 months [95% CI 1·9–2·9] vs 1·9 months [1·9–2·2]; hazard ratio [HR] 0·82 [95% CI 0·68–1·00], p=0·0427). At the time of the primary analysis of overall survival (median follow-up 18·4 months [IQR 13·8–22·4]), overall survival was significantly greater in the afatinib group than in the erloinib group (median 7·9 months [95% CI 7·2–8·7] vs 6·8 months [5·9–7·8]; HR 0·81 [95% CI 0·69–0·95], p=0·0077), as were progression-free survival (median 2·6 months [95% CI 2·0–2·9] vs 1·9 months [1·9–2·1]; HR 0·81 [95% CI 0·69–0·96], p=0·0103) and disease control (201 [51%] of 398 patients vs 157 [40%] of 397; p=0·0020). The proportion of patients with an objective response did not differ significantly between groups (22 [6%] vs 11 [3%]; p=0·0551). Tumour shrinkage occurred in 103 (26%) of 398 patients versus 90 (23%) of 397 patients. Adverse event profiles were similar in each group: 224 (57%) of 392 patients in the afatinib group versus 227 (57%) of 395 in the erlotinib group had grade 3 or higher adverse events. We recorded higher incidences of treatment-related grade 3 diarrhoea with afatinib (39 [10%] vs nine [2%]), of grade 3 stomatitis with afatinib (16 [4%] vs none), and of grade 3 rash or acne with erlotinib (23 [6%] vs 41 [10%]). Interpretation The significant improvements in progression-free survival and overall survival with afatinib compared with erlotinib, along with a manageable safety profile and the convenience of oral administration suggest that afatinib could be an additional option for the treatment of patients with squamous cell carcinoma of the lung. Funding Boehringer Ingelheim.
copEngland
pubElsevier Ltd
pmid26156651
doi10.1016/S1470-2045(15)00006-6