LUX-Lung 7 Trial Demonstrates Efficacy of Afatinib Over Gefitinib

Second-generation, EGFR-directed therapy afatinib (Gilotrif) may be superior to first-generation gefitinib (Iressa) in reducing the risk of disease progression and treatment failure in first-line treatment of patients with EGFR mutation-positive, advanced non-small cell lung cancer (NSCLC), according to new results from the LUX-Lung 7 clinical trial. The phase IIb trial met two of its co-primary endpoints of progression-free survival (PFS) by independent review and time-to-treatment failure.

The results, which were presented January 27, 2016, at the 14th Annual British Thoracic Oncology Group (BTOG) Conference in Dublin, Ireland, showed afatinib significantly reduced the risk of lung cancer progression by 27% compared to gefitinib. Investigators found that more patients on afatinib were free of cancer growth at 18 months after starting treatment (27% versus 15%), and the same was true at 24 months after the start of treatment (18% versus 8%). Data for the third co-primary endpoint, overall survival (OS), are not yet mature and will be presented in the future.

The researchers reported that significantly more patients had an objective tumor response with afatinib when compared to gefitinib (70% versus 56%), with a median duration of response of 10.1 months for afatinib and 8.4 months for gefitinib. The improvement in PFS with afatinib was consistent across most predefined clinical subgroups, including gender, age, race, and EGFR mutation type.

“As the first global head-to-head trial directly comparing two EGFR-directed therapies for the treatment of patients with EGFR mutation-positive NSCLC, LUX-Lung 7 marks a significant milestone to better understanding the benefits of first-line treatment options for this population,” said Shirish Gadgeel, MD, who is the leader of the Thoracic Oncology Multidisciplinary Team and president of the Medical Executive Committee of the Karmanos Cancer Center, Detroit, in a Boehringer Ingelheim press release.

The phase IIb trial included 319 patients with advanced stage NSCLC harboring common EGFR mutations (del19 or L858R) who received no prior treatment. The study showed that the overall frequency of patients experiencing serious adverse events and discontinuing treatment due to adverse events was similar in both arms.

Treatment with both afatinib and gefitinib in the LUX-Lung 7 trial was generally tolerable, leading to an equally low rate of treatment-related discontinuation in both arms (6.3%). The most common grade ≥3 related AEs with afatinib were diarrhea (12.5%) and rash/acne (9.4%). The most common grade ≥3 related AEs with gefitinib was AST/ALT increase (8.8%) and rash/acne (3.1%). Drug-related interstitial lung disease was reported in four patients on gefitinib and no patients on afatinib.

“Interestingly, the progression-free survival difference observed in the LUX-Lung 7 trial became more prominent over time so that the progression-free survival rate was more than doubled with afatinib at 24 months,” said Mehdi Shahidi, MD, Medical Head, Solid Tumor Oncology, Boehringer Ingelheim.