First-Line Afatinib versus Gefitinib in EGFRm+ Advanced NSCLC: Updated Overall Survival 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 TKI gefitinib are approved
for first-line treatment of advanced EGFRm+ NSCLC. This Phase IIb trial prospectively compared afatinib versus
gefitinib in this setting.

Methods: LUX-Lung 7 assessed afatinib (40 mg/day) versus gefitinib (250 mg/day) in treatment-naïve patients
with stage IIIb/IV NSCLC harboring a common EGFR mutation (Del19/L858R). Co-primary endpoints were PFS (independent review), time to treatment failure (TTF) and OS. Other endpoints included ORR and AEs. In case of grade 3/selected grade 2 drug-related AEs the afatinib dose could be reduced to 30 mg or 20 mg (minimum). The primary analysis of PFS/TTF was undertaken after w250 PFS events. The primary OS analysis was planned after w213 OS events and a follow-up period of 32 months.

Results: 319 patients were randomized (afatinib: 160; gefitinib: 159). At the time of primary analysis, PFS (HR [95% CI] 0.73 [0.57‒0.95], p¼0.017), TTF (0.73 [0.58‒0.92], p¼0.007) and ORR (70 vs 56%, p¼0.008) were significantly improved with afatinib versus gefitinib. The most common grade 3 AEs were diarrhea (13%) and rash/acne (9%) with afatinib and elevated ALT/AST (9%) with gefitinib. 42% of patients treated with afatinib had 1 dose reduction due to AEs; dose reductions were more common in females than males (77%/23%) and non-Asians than Asians (64%/36%). Dose reduction of afatinib did not negatively impact PFS (<40mg vs 40mg; HR [95% CI]: 1.34 [0.90‒2.00]) but reduced incidence and severity of drugrelated grade 3 AEs. Treatment discontinuation due to drug-related AEs was the same in each arm (6%). The data cut-off for primary OS analysis occurred on 8 April 2016. At this time, median treatment duration (range) was 13.7 (0‒46.4) versus 11.5 (0.5‒48.7) months with afatinib and gefitinib. 25% (afatinib) and 13% (gefitinib) of patients received treatment for >24 months. 73% and 77% of patients in the afatinib and gefitinib arms had 1 subsequent systemic anti-cancer treatment, with 46% and 56% receiving a subsequent EGFR-TKI including osimertinib (14%)/olmutinib (14%). OS data, including subgroup analysis with respect to subsequent therapy will be presented at the meeting.

Conclusion: Afatinib significantly improved PFS, TTF and ORR versus gefitinib in EGFRm+ NSCLC patients, with a manageable AE profile and few drug-related discontinuations. Dose adjustment of afatinib reduced drugrelated
AEs without compromising efficacy. Primary OS analysis will be reported.
All Author(s) ListKeunchil Park, Eng Huat Tan, Li Zhang, Vera Hirsh, Ken O'Byrne, Michael Boyer, James Chih-Hsin Yang, Tony Mok, Ki Hyeong Lee, Shun Lu, Yuankai Shi, Sang-We Kim, Janessa Laskin, Dong-Wan Kim, Scott Laurie, Karl Kölbeck, Jean Fan, Nigel Dodd, Angela Märten, Luis Paz-Ares
Name of ConferenceIASLC 17th World Conference on Lung Cancer Dec 4-7, 2016
Start Date of Conference04/12/2016
End Date of Conference07/12/2016
Place of ConferenceVienna
Country/Region of ConferenceAustria
Proceedings TitleJournal of Thoracic Oncology
Volume Number12
Issue NumberS1
PagesS335 - S336
LanguagesEnglish-United Kingdom
KeywordsAfatinib, Gefitinib

Last updated on 2021-19-10 at 00:47