Overall Survival Analysis of LUX-Lung 3 and LUX-Lung 6 Indicates Improvement With Afatinib in Subgroup of EGFR-Mutant Lung Cancer
In an analysis of overall survival in the phase III LUX-Lung 3 and LUX-Lung 6 trials reported in The Lancet Oncology, Yang et al found no significant difference between afatinib (Gilotrif) vs pemetrexed (Alimta)-cisplatin (LUX-Lung 3) or vs gemcitabine-cisplatin (LUX-Lung 6) in previously untreated, predominantly Asian patients with EGFR mutation-positive stage IIIB or IV lung adenocarcinoma. A significant difference favoring afatinib was found among patients with exon 19 deletion (del19) in both trials, with no difference observed among patients with the Leu858Arg mutation.
Study Details
In LUX-Lung 3 (N = 345) and LUX-Lung 6 (N = 364), patients EGFR-mutant disease were randomly assigned 2:1 to receive afatinib or chemotherapy. Overall, 72% of patients in LUX-Lung 3 and 100% in LUX-Lung 6 were Asian. Approximately 50% of patients in LUX-Lung 3 and 51% of patients in LUX-Ling 6 had the del19 mutation, and approximately 40% and 39% had the Leu858Arg mutation. Both trials showed improved progression-free survival, the primary endpoint, with afatinib treatment. Improvement in progression-free survival was greatest among patients with the del19 mutation.
Overall Survival
In the overall survival analysis, median follow-up was 41 months in LUX-Lung 3 and 33 months in LUX-Lung 6. Median overall survival among all patients was 28.2 months in the afatinib group vs 28.2 months in the chemotherapy group (hazard ratio [HR] = 0.88, P = .39) in LUX-Lung 3 and 23.1 vs 23.5 months (HR = 0.93, P = .61) in LUX-Lung 6.
Among patients with the del19 mutation, median overall survival was 33.3 vs 21.1 months (HR = 0.54, P = .0015) in LUX-Lung 3 and 31.4 vs 18.4 months (HR = 0.64, P = .023) in LUX-Lung 6.
Among patients with the Leu858Arg mutation, median overall survival was 27.6 vs 40.3 months (HR = 1.30, P = .29) in LUX-Lung 3 and 19.6 vs 24.3 months (HR = 1.22, P = .34) in LUX-Lung 6.
The investigators concluded: “Although afatinib did not improve overall survival in the whole population of either trial, overall survival was improved with the drug for patients with del19 EGFR mutations. The absence of an effect in patients with Leu858Arg EGFR mutations suggests that EGFR del19-positive disease might be distinct from Leu858Arg-positive disease and that these subgroups should be analysed separately in future trials.”
James Chih-Hsin Yang, MD, of National Taiwan University, is the corresponding author for The Lancet Oncology article.
The study was funded by Boehringer Ingelheim. For full disclosures of the study authors, visit www.thelancet.com.
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