Afatinib Improves Progression-Free Survival vs Erlotinib in Second-Line Treatment of Advanced Squamous Cell Carcinoma of the Lung
In the phase III LUX-Lung 8 trial reported in The Lancet Oncology, Soria et al found that the irreversible ErbB-family inhibitor afatinib (Gilotrif) significantly improved progression-free and overall survival vs the EGFR tyrosine kinase inhibitor erlotinib as second-line treatment in patients with stage IIIB or IV squamous cell carcinoma of the lung who had disease progression after four or more cycles of platinum-based chemotherapy.
Study Details
In this open-label trial, 795 patients from 23 countries were randomly assigned between March 2012 and January 2014 to receive afatinib at 40 mg/d (n =398) or erlotinib at 150 mg/d (n = 397). The primary endpoint was progression-free survival on independent central review in the intent-to-treat population.
The afatinib and erlotinib groups were generally balanced for baseline characteristics, including age (median, 65 and 64 years), sex (84% and 83% male), ethnic origin (22% East Asian in both, 88% other in both), smoking status (94% and 95% ever), and stage (IIIB in 12% in both, IV in 88% and 87%).
Progression-Free and Overall Survival
Median follow-up was 6.7 months at the primary analysis of progression-free survival, at which point enrollment was not yet complete. Median progression-free survival was 2.4 months (95% confidence interval [CI] = 1.9–2.9 months) in the afatinib group vs 1.9 months (95% CI = 1.9–2.2 months) in the erlotinib group (hazard ratio [HR] = 0.82, P = .0427).
Median follow-up at the time of primary analysis of overall survival was 18.4 months. Median overall survival was 7.9 months (95% CI = 7.2–8.7 months) vs 6.8 months (95% CI = 5.9–7.8 months; HR = 0.81, P = .0077). At this time point, median progression-free survival was 2.6 months (95% CI = 2.0–2.9 months) vs 1.9 months (95% CI = 1.9–2.1 months; HR = 0.81, P = .0103), and disease control rates were 51% vs 40% (P = .0020). Progression-free and overall survival benefit of afatinib was observed across most subgroups. Objective response was observed in 6% vs 3% (P = .0551).
Overall, 46% of the afatinib group and 49% of the erlotinib group received one or more lines of subsequent treatment, with the most common being docetaxel (24% and 26%) and gemcitabine (10% and 11%).
Adverse Events
Grade ≥ 3 adverse events occurred in 57% of afatinib patients and 57% of erlotinib patients. Treatment-related grade 3 diarrhea (10% vs 2%) and stomatitis (4% vs 0%) were more common with afatinib, and treatment-related grade 3 rash/acne (10% vs 6%) was more common with erlotinib.
Serious adverse events occurred in 44% of patients in both groups. Adverse events led to dose reduction in 27% vs 14% of patients and to discontinuation in 20% vs 17%. Six deaths in the afatinib group and five in the erlotinib group were considered treatment-related.
The investigators concluded: “The significant improvements in progression-free survival and overall survival with afatinib compared with erlotinib, along with a manageable safety profile and the convenience of oral administration suggest that afatinib could be an additional option for the treatment of patients with squamous cell carcinoma of the lung.”
Jean-Charles Soria, MD, of Gustave Roussy Cancer Campus and University Paris-Sud, 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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