Outcome to erlotinib in non-small cell lung cancer (NSCLC) patients (p) with EGFR in-frame deletions of exon 19 according to the size of the deletion.

Abstract

7549 Background: In-frame deletions of exon 19 n est around the LREA string of amino acids (aa) located between residu es 747-750 of the EGFR polypeptide. Although outcome to erlotinib has been associated with the pr esence of the exon 19 deletion, the potential influence of the number of aa deleted has not been previously examined. Methods: 118 NSCLC p with EGFR in-frame deletions in exon 19 were treated with erlotinib. EGFR deletions were detected in pretreatment biopsies by length analysis after PCR and confirmed by DNA sequencing. Outcome to erlotinib was correlated with the size of the deletion. Results: p were classified in 4 subgroups according to the number of aa deleted: 6 aa in 60 p, 7 aa in 10 p, 5 aa in 9 p, and other aa variations in 39 p. No differenc es were observed among the 4 subgroups according to gender, smoking history, PS, metastatic site (including brain, bone, liver, pleural or adrenal), or other clinical characteristics. R esponse rate was 74.5% in the 6-aa subgroup, 83.3% in the 7-aa subgroup; 88.9% in the 5-aa subgroup, and 82.4% in others (p = 0.67). Progression-free survival was 19 months (m), 14 m, 11 m and 13 m respectively (p = 0.97). Median survival was 31 m, not reached, 24 m and 28 m, r espectively (p = 0.97). The frequency of grade 3-4 skin toxicity was higher in the 7-aa subgroup (20%; p = 0.09), but no other differences in skin or gastrointestinal toxicity were observed. Conclusions: Although the size of the deletion did not predict differenc es in outcome to erlotinib, the efficacy of other novel targeted agents may prove to be influenced by the size of the deletion. In future studies of p with EGFR mutations, it would thus be advisable to report the exact position of the deletion and the number of aa deleted. No significant financial relationships to disclose.