P3.02b-083 Potential Usage of Afanitib in the Treatment of Non-Small-Cell Lung Cancer with Uncommon EGFR Mutations: Topic: EGFR Clinical

The frequency of EGFR mutations is said to be relatively high within East Asian population. The most common EGFR mutations such as exon 19 deletions and exon 21 L858R mutation are strong predictors of good response to EGFR-TKIs in non-small-cell lung cancer. Exon 20 T790M mutation which accounts for a large part of 1st and 2nd generation EGFR-TKI resistance, is well known to be detected after failure of prior EGFR-TKI therapy. Furthermore, T790M mutation is a predictor of good response to osimertinib, 3rd generation EGFR-TKI. Meanwhile, other uncommon EGFR mutations are identified, such as exon 18 G719X mutation, exon 20 S768I mutation, and exon 21 L861Q mutation. LUX-Lung study reported afatinib may be effective for these uncommon EGFR mutations, however, their treatments are still controversial and their resistance-gaining mechanisms to EGFR-TKI are also unknown. We analyzed the clinical data and the effectiveness of EGFR-TKIs (gefitinib, erlotinib, and afatinib) in patients with common and uncommon EGFR mutations in Fukuchiyama City Hospital. Eighteen patients had uncommon EGFR mutations, which included 13 patients with G719X mutation, four patients with S768I mutation, and one patient with L861Q mutation. Smokers were seen more frequently in patients with G719X mutation in contrast to patients with common EGFR mutations (85% vs 28%, P=0.002). No smoker was found in patients with S768I mutation. Of all patients with uncommon EGFR mutations, 12 patients were treated with EGFR-TKIs. Response rates of 1st generation EGFR-TKI (gefitinib or erlotinib) and afatinib were 33% (2/6) and 67% (4/6), respectively. Three patients underwent rebiopsy after failure of treatment with afanitib. In two patients with G719X mutation, the mutation disappeared at rebiopsy. In one patient with S768I mutation, new G719X mutation was detected in addition to S768I mutation. Uncommon EGFR mutations could be used as predictors of better response to afatinib, the 2nd generation EGFR-TKI. However, uncommon EGFR mutations are clinically heterogeneous. For instance, our data suggest that smoking be associated with G719X mutation, but not with S768I mutation. Further prospective researches are needed to establish the standard therapy for each uncommon EGFR mutation.