Approximately 10–12% of patients with EGFRm+ NSCLC have tumours harbouring uncommon EGFR mutations. Preclinical data indicate that the ErbB family blocker, afatinib, has broader inhibitory activity against uncommon mutations, including compound mutations, compared with first-generation EGFR TKIs.1,2 Post-hoc analysis of the LUX-Lung 2/3/6 trials3 demonstrated that afatinib is active against certain uncommon EGFR mutations; the ORR against G719X (n=18), L861Q (n=16) and S768I (n=8) single/compound mutations was 78%, 56% and 100%. Patients with exon 18–21 uncommon mutations had PFS and OS of 10.7 and 19.4 months. The aim of this analysis was to explore the sensitivity of uncommon EGFR mutations to afatinib in a broader ‘real world’ patient population.
We have undertaken a pooled analysis of an Asian phase IIIB trial (NCT01953913) and a German non-interventional study (NCT02047903) that assessed afatinib in patients with TKI-naïve EGFRm+ NSCLC. Tumour response was based on investigator review; PFS was calculated by Kaplan-Meier methodology.
Fifty-four patients were identified with uncommon mutations, including L861Q (n=13), S768I (n=3), G719X (n=23), other (n=8); 21 patients had compound mutations. Patients baseline characteristics were: male: 59%; median age (range): 63.5 (35‒79) years; ECOG PS 0 or 1/>1: 93%/6%. Combined ORR in evaluable patients with L861Q, S768I or G719X was 59% (20/34); ORR for the individual mutations in patients with G719X, L861Q or compound mutations was 58%, 57% and 47%, respectively. Overall, PFS in patients with L861Q, S768I or G719X was 10.7 months (L861Q: 10.7 months; G719X: 10.6 months; compound mutations: 7.3 months).
In a ‘real world’ cohort of patients with EGFRm+ NSCLC, afatinib was active against uncommon mutations known to be less responsive to reversible EGFR TKIs. These data are in line with the LUX-Lung trials and support the use of afatinib in patients with non-resistant EGFR mutations.