LUX-Lung 8 clinical trial

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 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


Randomisation 1:1

Afatinib 40 mg Oral once daily
Erlotinib 150 mg Oral once daily


Primary Outcome Measure:

  • 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
  • Safety
  • 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).

Hazard ratio = 0.81 95%CI = 0.69–0.96
LUX-Lung 8: figure for progression-free survival (PFS) with afatinib vs erlotinib


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

LUX-Lung 8: figure for overall survival (OS) with afatinib vs erlotinib


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.

LUX-Lung 8: figure for objective response rate (ORR) with afatinib vs erlotinib


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:

For afatinib:

  • Diarrhoea (Grade 3=10%)
  • Rash/acne (Grade 3=6%)
  • Stomatitis (Grade 3=4%)
  • Fatigue (Grade 3=2%)

For erlotinib:

  • Rash/acne (Grade 3=10%)
  • Diarrhoea (Grade 3=2%)
  • Fatigue (Grade 3=2%)
  • Pruritus (Grade 3=0%)

Treatment-related Grade 3 diarrhoea and stomatitis were higher with afatinib than with erlotinib, while Grade 3 rash/acne was higher with erlotinib than with afatinib. 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).

LUX-Lung 8: HRQoL chart for improvement in patient symptoms with afatinib vs erlotinib

Biomarker analysis:

No tumour biomarkers have been identified that are predictive of a clinical outcome with afatinib or erlotinib for treatment of SqCC of the lung. 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 of the lung 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).


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4 (Accessed: July 2017).

*Afatinib is approved in more than 80 markets including the EU, Japan, Taiwan, and Canada under the brand name GIOTRIF®, in the US under the brand name GILOTRIF® and in India under the brand name Xovoltib®; for the full list please see here. Registration conditions differ internationally; please refer to locally approved prescribing information.