Afatinib versus Gefitinib as First-Line Treatment for EGFR Mutation-Positive NSCLC Patients Aged ≥75 Years: Subgroup Analysis of LUX-Lung 7
Invited conference paper presented and published in conference proceedings


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AbstractBackground: The irreversible ErbB family blocker afatinib and the reversible EGFR tyrosine kinase inhibitor
gefitinib are approved for first-line treatment of advanced EGFRm+ NSCLC. In the Phase IIb LUX-Lung 7
trial, afatinib significantly improved median progressionfree survival (PFS; HR¼0.73 [95% CI, 0.57e0.95],
p¼0.017), objective response rate (70% vs 56%, p¼0.008) and time to treatment failure (TTF; HR¼0.73
[95% CI, 0.58e0.92], p¼0.007) versus gefitinib in this setting (Park et al. Lancet Oncol 2016). Here we evaluated
the efficacy and safety of afatinib versus gefitinib in patients aged 75 years in a subgroup analysis of LUXLung
7 (NCT01466660). Median PFS for both age groups was in line with the overall population and favored afatinib versus gefitinib (patients 75 years: 14.7 vs 10.8 months, HR¼0.69 [95% CI, 0.33e1.44]; patients <75 years: 11.0 vs 10.9
months, HR¼0.76 [95% CI, 0.58e1.00]). The incidence of treatment-related AEs (grade 3/4) was slightly higher
in the older subgroup (afatinib: 42%/0%; gefitinib: 24%/5%) than in the younger subgroup (afatinib: 28%/
2%; gefitinib: 15%/<1%). There were no unexpected safety findings. The most common treatment-related AEs
(all grade [grade 3]) with afatinib in the older patient subgroup were diarrhea (89% [21%]), rash (63% [5%]),
dry skin (37% [0%]), and decreased appetite (32% [0%]). Dose reduction/discontinuation of afatinib due to
treatment-related AEs was required in 53%/16% and 40%/5% of the older and younger subgroup, respectively.
Conclusion: A small subgroup of patients in the LUXLung 7 trial were 75 years old (13%). In exploratory
subgroup analyses of patients aged 75 and <75 years old, advancing age did not adversely affect the PFS
benefit and tolerability observed with afatinib versus gefitinib in treatment-naïve EGFRm+ NSCLC patients.
These findings suggest that afatinib can provide an effective and tolerable treatment for older patients with
EGFRm+ NSCLC.
Methods: Treatment-naïve patients with stage IIIB/IV EGFRm+ NSCLC were randomized (1:1) to oral afatinib
(40 mg/day) or gefitinib (250 mg/day), stratified by EGFR mutation type (Del19/L858R) and presence of brain metastases (Yes/No). Co-primary endpoints were PFS, TTF, and overall survival. Subgroup analyses of PFS
and adverse events (AEs) by age (75/<75 years) were exploratory.
Results: Of 319 patients randomized in LL7, 40 (13%) were aged 75 years (afatinib n¼19, gefitinib n¼21). Median PFS for both age groups was in line with the overall population and favored afatinib versus gefitinib (patients 75 years: 14.7 vs 10.8 months, HR¼0.69 [95% CI, 0.33e1.44]; patients <75 years: 11.0 vs 10.9 months, HR¼0.76 [95% CI, 0.58e1.00]). The incidence of treatment-related AEs (grade 3/4) was slightly higher in the older subgroup (afatinib: 42%/0%; gefitinib: 24%/5%) than in the younger subgroup (afatinib: 28%/2%; gefitinib: 15%/<1%). There were no unexpected safety findings. The most common treatment-related AEs (all grade [grade 3]) with afatinib in the older patient subgroup were diarrhea (89% [21%]), rash (63% [5%]), dry skin (37% [0%]), and decreased appetite (32%
[0%]). Dose reduction/discontinuation of afatinib due to treatment-related AEs was required in 53%/16% and
40%/5% of the older and younger subgroup, respectively.
Conclusion: A small subgroup of patients in the LUXLung 7 trial were 75 years old (13%). In exploratory subgroup analyses of patients aged 75 and <75 years old, advancing age did not adversely affect the PFS benefit and tolerability observed with afatinib versus gefitinib in treatment-naïve EGFRm+ NSCLC patients. These findings suggest that afatinib can provide an effective and tolerable treatment for older patients with EGFRm+ NSCLC.
All Author(s) ListKeunchil Park, Eng Huat Tan, Li Zhang, Vera Hirsh, Ken O’Byrne, Michael Boyer, James Chih-Hsin Yang, Tony Mok, Barbara Peil, Angela Märten, Luis Paz-Ares
Name of ConferenceIASLC 17th World Conference on Lung Cancer
Start Date of Conference04/12/2016
End Date of Conference07/12/2016
Place of ConferenceVienna
Country/Region of ConferenceGermany
Proceedings TitleJournal of Thoracic Oncology
Series TitlePoster Session 3
Number in SeriesP3.02B-044
Year2017
Month1
Volume Number12
Issue NumberS1
Pagess1214
LanguagesEnglish-United Kingdom
Keywordsafatinib, NSCLC

Last updated on 2018-18-01 at 08:19