ErbB mutations in patients with squamous NSCLC:
The LUX-Lung 8 trial demonstrated clinical benefit with afatinib versus erlotinib in the second-line treatment of a broad patient population with advanced squamous non-small cell lung cancer (NSCLC).1
With the objective of identifying specific populations that might obtain particular benefit from second-line afatinib, Goss and colleagues explored ErbB Family mutations as potential oncogenic drivers in patients from the LUX-Lung 8 trial with squamous NSCLC.2 Next-generation sequencing revealed a relatively high prevalence of ErbB Family mutations in patients with squamous NSCLC, 53 of 245 patients (21.6%).2 In this subpopulation, progression-free survival (PFS) and overall survival (OS) were longer with afatinib* than erlotinib in patients with ErbB wild-type tumours (median PFS: 3.5 vs 2.5 months; hazard ratio[HR]=0.69, 95% confidence interval [CI]: 0.51–0.92; p=0.012 and median OS: 8.4 vs 6.6 months; HR=0.81, 95% CI: 0.62–1.05; p=0.115).2 Afatinib treatment effects were more pronounced in patients with ErbB mutation-positive squamous NSCLC than in those without ErbB mutations (median PFS: 4.9 vs 3.0 months; HR=0.62, 95% CI: 0.37–1.02; p=0.062 and median OS: 10.6 vs 8.1 months; HR=0.75, 95% CI: 0.47–1.17; p=0.206, respectively).2 The most marked treatment differences were seen in 12 patients with HER2 mutations, in whom the presence of HER2 mutations predicted more favourable outcomes with afatinib than erlotinib in terms of both PFS (interaction p value = 0.006) and OS (interaction p value = 0.003).2
Overall, the authors concluded that the role of ErbB mutations in squamous lung cancer may warrant further investigation, particularly in patients with HER2 mutations.2 In a related commentary in JAMA Oncology, Professor Gandara and colleagues endorse this conclusion, particularly in light of the lack of targeted therapies available for patients with advanced squamous lung cancers and the increasing use of broad-based next-generation sequencing at time of NSCLC diagnosis, regardless of histology or smoking status.3
Soria J-C, et al. Lancet Oncol 2015;16(8):897‒907.
Goss GD, et al. JAMA Oncol 2018;4(9):1189‒97.
Gandara DR, et al. JAMA Oncol 2018;4(9):1197‒8.
*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 click here. Registration conditions differ internationally; please refer to locally approved prescribing information.
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Page last updated: March 2019
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