Afatinib Effective in NSCLC Patients With Rare EGFR Mutations

In patients with advanced non-small cell lung cancer (NSCLC), the effectiveness of certain treatments varies when it comes to rare epidermal growth factor receptor (EGFR) mutations found in tumors. In an analysis of three lung cancer trials, the phase II trial (LUX-Lung 2) and randomized phase III trials (LUX-Lung 3 and LUX-Lung 6), researchers analyzed data from patients that had been given afatinib (Gilotrif), a tyrosine kinase inhibitor. This was first reported in The Lancet Oncology.¹  

Afatinib is indicated for the first-line treatment of patients with metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations. But these particular trials examined the clinical activity of afatinib in NSCLC patients harboring rare EGFR mutations.

Six hundred patients across the three trials were prescribed afitinib in an effort to help block tumor growth--of those, 75 patients had uncommon EGFR mutations (38 in group one, 14 in group two, 23 in group three). Twenty-seven patients (71.1%, 95% confidence interval [CI]: 54.1–84.6) in group one experienced objective responses, as did two (14.3%, 95% CI: 1.8–42.8) in group two, and two (8.7%, 95% CI: 1.1–28.0) in group three. Median progression-free survival (PFS) was 10.7 months (95% CI: 5.6–14.7) in group one, 2.9 months (95% CI: 1.2–8.3) in group two, and 2.7 months (95% CI: 1.8–4.2) in group three. Median overall survival (OS) was 19.4 months (95% CI: 16.4–26.9) in group one, 14.9 months (8.1–24.9) in group two, and 9.2 months (4.1–14.2) in group three. 

The analysis showed that afatinib was active in NSCLC tumors that harbored certain types of uncommon EGFR mutations, specifically Gly719Xaa, Leu861Gln, and Ser768Ile, but less active in other mutations types. Patients with de novo Thr790Met and exon 20 insertion mutations experienced less clinical benefit.

Considering NSCLC is the most common of all lung cancers--accounting for approximately 85% of lung malignancies²--the data obtained from these three trials seems promising for patients with advanced disease and/or rare EGFR mutations who may not have many treatment options available.

All three LUX-lung cancer clinical trials (NCT00525148, NCT00949650, NCT01121393) are ongoing, but no longer recruiting patients.

References:

• Yang JCH, Sequist LV, Geater SL, et al. (2015). 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. The Lancet Oncology.
• American Cancer Society. (2014). Lung Cancer (Non-Small Cell).