ESMO 2014 - Abstract 1222O

ESMO 2014 Abstract 1222O:  A randomized, open-label, phase III trial of afatinib (A) vs erlotinib (E) as second-line treatment of patients (pts) with advanced squamous cell carcinoma (SCC) of the lung following first-line platinum-based chemotherapy: LUX-Lung 8 (LL8)

Goss, Glenwood et al.

Background: The use of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI) in patients with EGFR non mutated patients (EGFR WT) is controversial. NCIC BR 21 showed efficacy in the second and third line setting after a platinum doublet. This was independent of the EGFR mutation (EGFR M+). A survival advantage was seen in male smokers with squamous cell carcinoma who are very unlikely to harbour an EGFR mutation. None the less, EGFR TKI are restricted in many countries to only patients whose tumours harbour an EGFR mutation.

Methods: Patients with stage lV squamous cell carcinoma after progressing on a platinum doublet were randomized to afatinib or erlotinib.

Results: The primary endpoint of progression free survival was met with afatinib PFS 2.4 months vs 1.9 months for erlotinib (Figure 1).  The response rate was low but in those patients who responded, a durable benefit was seen.

ESMO 2014 Abstract graph --04.jpg

Conclusion: LL8 is the largest prospective trial to compare EGFR TKIs in pts with relapsed/refractory SCC. PFS and DCR were significantly better for A than E. AEs were comparable and consistent with the mechanistic profile of EGFR inhibition.

CARE Faculty Perspective: Although the improvement in survival is short, this is an important trial to take note of. EGFR TKI's are restricted in many countries to only patients with an EGFR mutation. The NCIC BR 21 trial showed this class of drugs is active in a non-mutated population after a platinum doublet. LUX Lung 8 confirms this. Afatinib is an option in the second and third line setting in an EGFR WT patient and confers a survival advantage of the standard of care of erlotinib in this setting.  

Barb Melosky, MD