In Lung Cancer, Afatinib Active in Certain Uncommon EGFR Mutations

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Afatinib has activity against NSCLC tumors that harbor certain uncommon mutations.
Afatinib has activity against NSCLC tumors that harbor certain uncommon mutations.

Afatinib has activity against non-small cell lung carcinoma (NSCLC) tumors that harbor certain uncommon mutations, according to a combined post-hoc analysis published online ahead of print this week in the journal The Lancet Oncology.  

This post-hoc analysis is a combination of a phase 2 trial (LUX-Lung 2) and two phase 3 trials (LUX-Lung 3 and LUX-Lung 6) that looked into tyrosine kinase inhibitor-naive patients with EGFR mutations in advanced NSCLC. The researchers enrolled 600 patients and randomly assigned them to receive afatinib.

Based on the mutation status, the patients were then categorized into group 1 (point mutations or duplications in exons 18–21), group 2 (e-novo Thr790Met mutations in exon 20 alone or in combination with other mutations), or group 3 (exon 20 insertions). The most frequent uncommon mutations, Gly719Xaa, Leu861Gln, and Ser768Ile, were also assessed.  

Out of 75 (12%) patients with uncommon EGFR mutations, the patients in group 1 had an objective response rate of 71.1% (95% CI: 54.1, 84.6), followed by 14.3% (95% CI: 1.8, 42.8) in group 2 and 8.7% (95% CI: 1.1, 28.0) in group 3.

Median progression-free survival was 10.7 months (95% CI: 5.6, 14.7) in group 1, 2.9 months (95% CI: 1.2, 8.3) in group 2 and 2.7 months (95% CI: 1.8, 4.2) in group 3.

Median overall survival was 19.4 months (95% CI: 16.4, 26.9) in group 1, 14.9 months (8.1, 24.9) in group 2, and 9.2 months (4.1, 14.2) in group 3.

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For the most frequent uncommon mutations, 77.8% (95% CI: 52.4, 93.6) of the patients with Gly719Xaa had an objective response, followed by 56.3% (95% CI: 29.9, 80.2) with Leu861Gln, and 100% (95% CI: 63.1, 100.0) with Ser768Ile.

The findings suggest that afatinib is active against most frequent uncommon mutations (Gly719Xaa, Leu861Gln, and Ser768Ile) and ultimately can help clinical decisions for the patients with advanced NSCLC tumors that harbor uncommon EGFR mutations.


  1. Yang C-H, Sequist LV, Geater SL, et al. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015. [Epub ahead of print]. doi: 10.1016/S1470-2045(15)00026-1.

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