LUX-Lung 8 – A Phase III Trial of Afatinib* vs Erlotinib for the Treatment of Squamous Cell Lung Cancer After at Least One Prior Platinum-Based Chemotherapy

A randomised, open-label, Phase III trial of afatinib vs erlotinib in patients with advanced squamous cell carcinoma (SqCC) of the lung as second-line therapy following first-line platinum-based chemotherapy.

Trial CTgov-Identifier: NCT01523587


Stage IIIB/IV non-small cell lung cancer (NSCLC) of squamous histology
Completed at least four cycles of platinum-based doublet chemotherapy as first-line treatment
No prior treatment with epidermal growth factor receptor (EGFR) directed small molecules or antibodies
Eastern Cooperative Oncology Group performance status of 0–1

N = 795

Randomisation 1:1

  • Afatinib 40 mg
    Oral once daily

  • Erlotinib 150 mg
    Oral once daily


Primary Outcome Measures:
Progression-free survival (PFS) assessed by independent central review 

Key Secondary Outcome Measure:
Overall survival (OS) 

Other Secondary Outcome Measures: 
Objective response rate (ORR)
Disease control rate (DCR)
Tumour shrinkage 
Health-related quality of life (HRQoL)


Median PFS was 2.6 months in patients receiving afatinib compared with 1.9 months in patients receiving erlotinib (p=0.0103).

OS was significantly improved with afatinib vs erlotinib (p=0.0077).

Overall survival

ORR and tumour shrinkage were significantly better in patients receiving afatinib vs erlotinib. In addition, duration of response was 7.3 months for afatinib and 3.7 months for erlotinib.

Objective responsel


Adverse event (AE) profiles were similar with both treatments and 57% of patients in each group had Grade ≥3 AEs. The most common AEs were diarrhoea, rash/acne, fatigue and stomatitis in the afatinib group, and rash/acne, diarrhoea, fatigue and pruritus in the erlotinib group. Treatment-related Grade 3 diarrhoea and stomatitis were higher with afatinib than with erlotinib (10.0% vs 2.0% and 4.0% vs 0.0%, respectively), while Grade 3 rash/acne was higher with erlotinib than with afatinib (10.0% vs 6.0%). The safety profile of afatinib was similar in long-term responders (patients treated for ≥12 months), with no discontinuations due to AEs.

Patients receiving afatinib had significantly improved overall HRQoL compared with those receiving erlotinib (36% vs 28%, p=0.04).


Biomarker analysis:
No tumour biomarkers have been identified that are predictive of a clinical outcome with afatinib or erlotinib for treatment of SqCC. In the Lux-Lung 8 study, an exploratory biomarker analysis tested the predictive ability of VeriStrat®, a proprietary serum protein test that has previously shown prognostic and predictive utility for EGFR-targeted agents in NSCLC. Patients were stratified by VeriStrat® classification of ‘good’ (VS-G) or ‘poor’ (VS-P). In patients with relapsed/refractory SqCC afatinib conferred significantly longer OS compared with erlotinib in the VS-G group (11.5 vs 8.9 months; hazard ratio [HR]=0.79 [95% confidence interval (Cl): 0.63–0.98], p <0.0001). In afatinib treated patients OS was significantly improved in the VS-G group compared with the VS-P group (11.5 vs 4.7 months; HR=0.40 [95% Cl: 0.31–0.51], p<0.0001). The patients classified as VS-G were nearly four times as likely to survive ≥12 months.


Afatinib has clinical efficacy as second-line treatment for patients with SqCC of the lung. Afatinib reduced the risk of death compared with erlotinib and also improved PFS, HRQoL and symptom control.

Afatinib has now been approved for the treatment of patients with locally advanced or metastatic NSCLC of squamous histology progressing on or after platinum-based chemotherapy (country dependent: US after platinum-based chemotherapy; EU on or after platinum-based chemotherapy).


Soria JC, Felip E, Cobo M, et al. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. Lancet Oncol 2015;16(8):897–907.

Goss G, Lee KH, Felip E, et al. Evaluation of VeriStrat, a serum proteomic test, in the randomised, open-label, Phase 3 LUX-Lung 8 trial of afatinib versus erlotinib for the second-line treatment of advanced squamous cell carcinoma of the lung. Ann Oncol 2016;27(Suppl 6):1238P.

Felip E, Soria JC, Cobo M, et al. Second-line afatinib versus erlotinib for patients with squamous cell carcinoma of the lung (LUX-Lung 8): analysis of tumour and serum biomarkers. J Thorac Oncol 2017;12(Suppl):S1086–S1087 (Abstract #P3.02b-003). (Accessed: April 2017).