The drug afatinib (Giotrif) posted positive results following the Phase IIb Lux Lung 7 trial, pharmaceutical Boehringer Ingelheim has announced.
Afatinib demonstrated superiority to gefitinib 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. This included reducing the risk of lung cancer progression and the risk of treatment failure both by 27% compared to gefitinib.
Additionally, More patients on afatinib were free of cancer growth 18 and 24 months after the start of treatment (27% vs 15% and 18% vs 8%, respectively).
The overall frequency of patients experiencing serious adverse events and discontinuing treatment due to adverse events was similar in both arms.
The Phase IIb trial met two of its coprimary endpoints of progression-free survival (PFS) by independent review and time to treatment failure (a measure of time between start, and discontinuation of treatment for any reason). The LUX-Lung 7 trial results were presented at the 14th Annual British Thoracic Oncology Group (BTOG) Conference in Dublin, Ireland.
The improvement in PFS became more pronounced over time, with a significantly higher proportion of patients alive and progression-free at 18 months (27% vs 15%) and 24 months (18% vs 8%), showing a greater long-term benefit to using afatinib versus gefitinib.
In addition to superior PFS, patients on afatinib had a significantly longer time on treatment: risk of treatment failure reduced by 27%, versus gefitinib. Significantly more patients had an objective tumour response (a clinically meaningful decrease in tumour size) with afatinib when compared to gefitinib (70% vs 56%), with a median duration of response of 10.1 months and 8.4 months, respectively. The improvement in PFS with afatinib was consistent across most pre-defined clinical subgroups, including gender, age, race and EGFR mutation type.
LUX-Lung 7 lead investigator Professor Keunchil Park, director of Innovative Cancer Medicine Institute (ICMI) at Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea said: “LUX-Lung 7 is the first global trial directly comparing two EGFR-directed therapies and the results demonstrate the benefits of second-generation inhibitor afatinib, compared to first-generation drug, gefitinib, in first-line therapy. These results provide important guidance on the choice of first-line treatment for patients with EGFR mutation-positive lung cancer.”
Treatment with both afatinib and gefitinib was generally tolerable, leading to an equally low rate of treatment-related discontinuation in both arms (6.3%).
The overall frequency of serious AEs was similar for both (afatinib: 44.4% vs gefitinib: 37.1%); the most common grade 3 related AEs with afatinib were: diarrhea (12.5%) and rash/acne (9.4%), and with gefitinib: aspartate aminotransferase (AST)/alanine aminotransferase (ALT) increase (8.8%) and rash/acne (3.1%).1 Drug-related interstitial lung disease was reported for four patients on gefitinib and no patients on afatinib.
Commenting on the data, Professor Klaus Dugi, Medical Director and Managing Director, Boehringer Ingelheim UK & Ireland said: “LUX-Lung 7 is the second positive head-to-head trial of afatinib versus first-generation EGFR TKIs in lung cancer, showing that first- and second-generation EGFR targeted agents are not the same. Interestingly, the progression-free survival difference observed in the LUX-Lung 7 trial became more prominent over time so that by 24 months the rate of patients who were free of cancer growth was more than doubled with afatinib compared to gefitinib.
“This is welcome news for patients with lung cancer and will provide clinicians with additional supportive evidence to help them make the best treatment choice for their patients.”
Data for the third co-primary endpoint, overall survival (OS), are not yet mature and will be presented in the future.