LUX-Lung 8: Afatinib Tops Erlotinib in Squamous NSCLC

Afatinib outperformed erlotinib with regard to both progression-free and overall survival in squamous cell carcinoma (SCC) of the lung, according to a phase III randomized trial (abstract 8002) presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 29 to June 2 in Chicago.

“Squamous cell carcinoma of the lung remains a disease with high unmet medical need,” said Jean-Charles Soria, MD, PhD, of Gustave Roussy Cancer Center in Paris. Erlotinib is currently approved as second-line therapy in these patients, but Soria said that afatinib, an irreversible inhibitor of EGFR and HER1, HER2, and HER4, could “shut down in a broader manner the signal transduction.”

The LUX-Lung 8 trial randomized 795 patients with stage IIIB/IV SCC who progressed after first-line platinum doublet therapy; 398 patients received afatinib 40 mg/day and 397 received erlotinib 150 mg/day. The trial was stratified by east-Asian vs non-east-Asian patients, to mitigate any imbalance in treatment effect, Soria said.

The median ages in the afatinib and erlotinib groups was 65 and 64, most patients were male and most were Caucasian, and most were current or ex-smokers. The vast majority had pure squamous histology. The study’s primary 12-month progression-free survival endpoint was reported in 2014; it was positive in favor of afatinib, allowing the secondary analysis of overall survival to move forward.

With regard to overall survival, Soria said that “the curves separate early on, there is a consistent advantage that remains true across all time points, and there is a 19% reduction in the risk of death.”

The median overall survival was 7.9 months with afatinib and 6.8 months with erlotinib, for a hazard ratio (HR) of 0.81 (95% CI, 0.69–0.95; P = .0077). An updated progression-free survival analysis showed a median progression-free survival of 2.6 with afatinib vs 1.9 for erlotinib, for an HR of 0.81 (95% CI, 0.69–0.96; P = .0103).

Objective response numerically favored afatinib, Soria said, but noted that most of the advantage comes from an increase in stable disease with afatinib. The disease control rate was 50.5% for afatinib and 39.5% with erlotinib. Patient-reported outcomes also showed better symptom improvement-including coughing, dyspnea, and others-with afatinib.

Adverse events were generally balanced, and reflected previous experience with EGFR tyrosine kinase inhibitors (TKIs). There was more grade 3/4 diarrhea and grade 3 stomatitis with afatinib, and more grade 3 rash with erlotinib.

“We believe that afatinib should be the TKI of choice in second-line treatment of patients with SCC of the lung,” Soria concluded.

The discussant for the session, Gregory J. Riely, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York, agreed that afatinib should be the TKI of choice in this patient population, but questioned whether EGFR TKIs in general should be the drug of choice. When this trial began, he said, there were few other options, but recent work on drugs including nivolumab and the combination of ramucirumab and docetaxel suggests other approaches may be better.