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Afatinib versus gefitinib in patients with EGFR mutation-positive advanced non-small-cell lung cancer: overall survival data from the phase IIb LUX-Lung 7 trial

View Article: PubMed Central - PubMed

ABSTRACT

Background: In LUX-Lung 7, the irreversible ErbB family blocker, afatinib, significantly improved progression-free survival (PFS), time-to-treatment failure (TTF) and objective response rate (ORR) versus gefitinib in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Here, we present primary analysis of mature overall survival (OS) data.

Patients and methods: LUX-Lung 7 assessed afatinib 40 mg/day versus gefitinib 250 mg/day in treatment-naïve patients with stage IIIb/IV NSCLC and a common EGFR mutation (exon 19 deletion/L858R). Primary OS analysis was planned after ∼213 OS events and ≥32-month follow-up. OS was analysed by a Cox proportional hazards model, stratified by EGFR mutation type and baseline brain metastases.

Results: Two-hundred and twenty-six OS events had occurred at the data cut-off (8 April 2016). After a median follow-up of 42.6 months, median OS (afatinib versus gefitinib) was 27.9 versus 24.5 months [hazard ratio (HR) = 0.86, 95% confidence interval (CI) 0.66‒1.12, P = 0.2580]. Prespecified subgroup analyses showed similar OS trends (afatinib versus gefitinib) in patients with exon 19 deletion (30.7 versus 26.4 months; HR, 0.83, 95% CI 0.58‒1.17, P = 0.2841) and L858R (25.0 versus 21.2 months; HR 0.91, 95% CI 0.62‒1.36, P = 0.6585) mutations. Most patients (afatinib, 72.6%; gefitinib, 76.8%) had at least one subsequent systemic anti-cancer treatment following discontinuation of afatinib/gefitinib; 20 (13.7%) and 23 (15.2%) patients received a third-generation EGFR tyrosine kinase inhibitor. Updated PFS (independent review), TTF and ORR data were significantly improved with afatinib.

Conclusion: In LUX-Lung 7, there was no significant difference in OS with afatinib versus gefitinib. Updated PFS (independent review), TTF and ORR data were significantly improved with afatinib.

Clinicaltrials.gov identifier: NCT01466660.

No MeSH data available.


Overall survival in patients with common EGFR mutations. Patients with exon 19 deletion (A) and patients with L858R mutation (B).CI, confidence interval; EGFR, epidermal growth factor receptor; HR, hazard ratio.
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mdw611-F2: Overall survival in patients with common EGFR mutations. Patients with exon 19 deletion (A) and patients with L858R mutation (B).CI, confidence interval; EGFR, epidermal growth factor receptor; HR, hazard ratio.

Mentions: OS with afatinib versus gefitinib was similar across prespecified subgroups of interest (Figure 1B). There was no significant OS difference between afatinib and gefitinib in pre-planned subgroups that were used as stratification factors, i.e. baseline brain metastases (presence versus absence) and EGFR mutation type (exon 19 deletion versus L858R). Median OS with afatinib versus gefitinib in patients with exon 19 deletions (30.7 versus 26.4 months; HR 0.83, 95% CI 0.58‒1.17, P = 0.2841; Figure 2A) and patients with the L858R mutation (25.0 versus 21.2 months; HR 0.91, 95% CI 0.62‒1.36, P = 0.6585; Figure 2B) was generally consistent with the overall EGFR mutation-positive study population. There was no interaction between OS and patient subgroups, except for age based on the cut-offs of <65 and ≥65 years (Figure 1B). However, further post-hoc analysis demonstrated a consistent trend for OS benefit with afatinib independent of age group (no interaction observed at cut-offs of 60, 70 or 75 years). Similar median OS with afatinib was seen at cut-offs of 60, 65, 70 and 75 years (supplementary Figure S1, available at Annals of Oncology online). Of note, subgroup sample sizes decreased with increasing age cut-off.Figure 2


Afatinib versus gefitinib in patients with EGFR mutation-positive advanced non-small-cell lung cancer: overall survival data from the phase IIb LUX-Lung 7 trial
Overall survival in patients with common EGFR mutations. Patients with exon 19 deletion (A) and patients with L858R mutation (B).CI, confidence interval; EGFR, epidermal growth factor receptor; HR, hazard ratio.
© Copyright Policy - cc-by-nc
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5391700&req=5

mdw611-F2: Overall survival in patients with common EGFR mutations. Patients with exon 19 deletion (A) and patients with L858R mutation (B).CI, confidence interval; EGFR, epidermal growth factor receptor; HR, hazard ratio.
Mentions: OS with afatinib versus gefitinib was similar across prespecified subgroups of interest (Figure 1B). There was no significant OS difference between afatinib and gefitinib in pre-planned subgroups that were used as stratification factors, i.e. baseline brain metastases (presence versus absence) and EGFR mutation type (exon 19 deletion versus L858R). Median OS with afatinib versus gefitinib in patients with exon 19 deletions (30.7 versus 26.4 months; HR 0.83, 95% CI 0.58‒1.17, P = 0.2841; Figure 2A) and patients with the L858R mutation (25.0 versus 21.2 months; HR 0.91, 95% CI 0.62‒1.36, P = 0.6585; Figure 2B) was generally consistent with the overall EGFR mutation-positive study population. There was no interaction between OS and patient subgroups, except for age based on the cut-offs of <65 and ≥65 years (Figure 1B). However, further post-hoc analysis demonstrated a consistent trend for OS benefit with afatinib independent of age group (no interaction observed at cut-offs of 60, 70 or 75 years). Similar median OS with afatinib was seen at cut-offs of 60, 65, 70 and 75 years (supplementary Figure S1, available at Annals of Oncology online). Of note, subgroup sample sizes decreased with increasing age cut-off.Figure 2

View Article: PubMed Central - PubMed

ABSTRACT

Background: In LUX-Lung 7, the irreversible ErbB family blocker, afatinib, significantly improved progression-free survival (PFS), time-to-treatment failure (TTF) and objective response rate (ORR) versus gefitinib in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Here, we present primary analysis of mature overall survival (OS) data.

Patients and methods: LUX-Lung 7 assessed afatinib 40&thinsp;mg/day versus gefitinib 250&thinsp;mg/day in treatment-na&iuml;ve patients with stage IIIb/IV NSCLC and a common EGFR mutation (exon 19 deletion/L858R). Primary OS analysis was planned after &sim;213 OS events and&thinsp;&ge;32-month follow-up. OS was analysed by a Cox proportional hazards model, stratified by EGFR mutation type and baseline brain metastases.

Results: Two-hundred and twenty-six OS events had occurred at the data cut-off (8 April 2016). After a median follow-up of 42.6 months, median OS (afatinib versus gefitinib) was 27.9 versus 24.5 months [hazard ratio (HR) = 0.86, 95% confidence interval (CI) 0.66&#8210;1.12, P&thinsp;=&thinsp;0.2580]. Prespecified subgroup analyses showed similar OS trends (afatinib versus gefitinib) in patients with exon 19 deletion (30.7 versus 26.4 months; HR, 0.83, 95% CI 0.58&#8210;1.17, P&thinsp;=&thinsp;0.2841) and L858R (25.0 versus 21.2 months; HR 0.91, 95% CI 0.62&#8210;1.36, P&thinsp;=&thinsp;0.6585) mutations. Most patients (afatinib, 72.6%; gefitinib, 76.8%) had at least one subsequent systemic anti-cancer treatment following discontinuation of afatinib/gefitinib; 20 (13.7%) and 23 (15.2%) patients received a third-generation EGFR tyrosine kinase inhibitor. Updated PFS (independent review), TTF and ORR data were significantly improved with afatinib.

Conclusion: In LUX-Lung 7, there was no significant difference in OS with afatinib versus gefitinib. Updated PFS (independent review), TTF and ORR data were significantly improved with afatinib.

Clinicaltrials.gov identifier: NCT01466660.

No MeSH data available.