Afatinib Improves Progression-Free Survival vs Cisplatin/Gemcitabine in First-Line Treatment of Asian Patients With Advanced EGFR-Mutant NSCLC
Afatinib (Gilotrif) improves progression-free survival compared with pemetrexed (Alimta)/cisplatin in first-line treatment of patients with EGFR mutation–positive advanced non–small cell lung cancer (NSCLC). In the phase III LUX-Lung 6 trial reported in The Lancet Oncology, Wu et al compared afatinib with gemcitabine/cisplatin, a regimen widely used in Asian countries, as first-line treatment in Asian patients in this setting. They found that afatinib significantly improved progression-free survival and objective response rate.
Study Details
In this open-label trial, performed at 36 centers in China, Thailand, and South Korea, 364 patients with treatment-naive EGFR mutation–positive stage IIIB or IV NSCLC were randomly assigned 2:1 to receive oral afatinib at 40 mg per day (n = 242) or gemcitabine at 1,000 mg/m2 on days 1 and 8 plus cisplatin 75 mg/m2 on day 1 of a 3-week schedule for up to six cycles (n = 122). The primary endpoint was progression-free survival assessed by independent central review in the intention-to-treat population.
The afatinib and gemcitabine/cisplatin groups were generally balanced for age (median, 58 years in both), sex (64% and 68% women), ethnic origin (90% Chinese in both), smoking history (75% and 81% never smoked, < 15 pack-years and stopped > 1 year ago for 3% in both, 22% and 16% other current or ex-smoker), Eastern Cooperative Oncology Group performance status (0 in 20% and 34%, 1 in 80% and 66%), and EGFR mutations (exon 19 deletions in 51% in both, Leu858Arg in 38% in both, and uncommon mutations in 11% and 11.5%).
Improved Progression-Free Survival
Median progression-free survival was significantly longer in the afatinib group than in the gemcitabine/cisplatin group on independent assessment (11.0 vs 5.6 months, hazard ratio [HR] = 0.28, P < .0001). Hazard ratios favored afatinib in all subgroups examined and were significant across subgroups for age, sex, EGFR mutation (except for uncommon mutations), and performance status and in nonsmokers (not in current or ex-smokers). In patients with common mutations, median progression-free survival was 11.0 vs 5.6 months (HR = 0.25, P < .0001).
Objective response was observed in 66.9% vs 23.0% of patients (odds ratio [OR] = 7.28, P < .0001). Overall survival data were immature at the time of the analysis (median, 22.1 months, 95% confidence interval [CI] = 20.0–not estimable, for afatinib vs 22.2 months, 95% CI = 18.0–not estimable, for gemcitabine/cisplatin; HR = 0.95, P = .76).
Totals of 58% of patients in the afatinib group and 61% in the gemcitabine/cisplatin group received postprogression treatment, including gemcitabine/cisplatin in 55% of the afatinib group and EGFR tyrosine kinase inhibitors in 48% of the gemcitabine/cisplatin group. Median times to deterioration of cough (not reached vs 10.3 months, HR = 0.45, P = .0001), dyspnea (7.7 vs 1.7 months, HR = 0.54, P < .0001), and pain (6.4 vs 3.4 months, HR = 0.70, P = .0265) were significantly prolonged with afatinib.
Adverse Events
Treatment-related adverse events of grade 3 or higher occurred in 36% of the afatinib group and 60% of the gemcitabine/cisplatin group. The most common treatment-related grade 3 or 4 adverse events were rash/acne (15%), diarrhea (5%), and stomatitis/mucositis (5%) in the afatinib group and neutropenia (26.5%), vomiting (19.5%), and leukopenia (15%) in the gemcitabine/cisplatin group.
Treatment-related serious adverse events occurred in 6% of afatinib patients and 8% of gemcitabine/cisplatin patients. Five afatinib-treated patients (2%) discontinued treatment due to rash or acne. The most common treatment-related adverse events resulting in treatment discontinuation in the gemcitabine/cisplatin group were vomiting (14%), nausea (10%), neutropenia (9%), and leukopenia (7%).
One death occurred in each group, due to sudden death in an afatinib patient and cardiac failure in a gemcitabine/cisplatin patient; both were considered potentially treatment-related by the investigator. One patient in the afatinib group had grade 4 treatment-related interstitial pneumonitis.
The investigators concluded, “First-line afatinib significantly improves progression-free survival with a tolerable and manageable safety profile in Asian patients with EGFR mutation–positive advanced lung NSCLC. Afatinib should be considered as a first-line treatment option for this patient population.”
Yi-Long Wu, MD, of Guangdong Academy of Medical Sciences, Guangzhou, China, 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.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
