LUX-Lung 1 was a phase IIb/III study that looked at the benefit of Afatinib ( Giotrif ) and best supportive care in comparison with placebo and best supportive care, as a third-line or fourth-line therapy in patients who had received a Platinum doublet and a first-generation tyrosine-kinase inhibitor ( TKI ) for at least 3 months.
A total of 697 patients with advanced, metastatic non-small-cell lung cancer were enrolled and 585 of them received Afatinib.
This study failed to demonstrate an overall survival benefit as its primary end point due to a higher median overall survival seen in the placebo arm.
The subsequent cancer treatment difference ( 257 [ 68% ] patients in the Afatinib group and 153 [ 79% ] patients in the placebo group ) may be attributable to the lack of a significant difference in overall survival between the two groups.
However, in a post hoc analysis, an improved overall survival of 5.8 months was reported with Afatinib in comparison with 4.6 months for placebo when the placebo group was controlled for no subsequent antitumor therapies ( hazard ratio, HR=0.65 ).
Although this study did not mandate the presence of EGFR mutations, 141 patient tissue samples were analyzed, and of these, 96 ( 68% ) showed the presence of EGFR-sensitizing mutations.
Median progression-free survival was longer in the Afatinib group than in the placebo group ( 3.3 months versus 1.1 months; HR=0.38, 95% CI 0.31–0.48, P less than 0.0001 ).
Afatinib was also studied in Japanese patients who had progressed on Erlotinib ( Tarceva ) and/or Gefitinib ( Iressa ) in LUX-Lung 4, a phase II single-arm study.
Sixty-two patients were enrolled in the study and 45 ( 72.6% ) were EGFR mutation-positive in their primary tumor according to local and/or central laboratory analyses.
Fifty-one ( 82.3% ) of these had acquired resistance to first-generation EGFR TKIs.
The median progression-free survival was 4.4 months ( 95% CI 2.8–4.6 ) and the median overall survival was 19.0 months ( 95% CI 14.9 to not achieved ).
Two patients meeting the resistance criteria with a secondary T790M mutation ( L858R + T790M and deletion exon 19 + T790M ) had stable disease for 9 months and one month, respectively.
Diarrhea and rash were the predominant adverse events with Afatinib. This trial showed a modest efficacy of Afatinib in a heavily pretreated lung cancer population. ( Xagena )
Joshi M et al, Cancer Manag Res 2015; 7: 75–82