Mutations of the catalytic subunit a of PI3K (PIK3CA) in erlotinib-treated non-small cell lung cancer (NSCLC) patients (p) with epidermal growth factor receptor (EGFR) mutations.

Abstract

7588 Background: Stage IV NSCLC p with EGFR mutations treated with erlotinib had a median progression-free survival (PFS) of 14 months (m) and median survival (MS) of 27 m in our experience. However, EGFR mutations can only imperfectly predict outcome. PIK3CA mutations occur in several tumors and have prognostic and therapeutic implications. We examined the presence and potential influence of PIK3CA mutations on outcome to erlotinib in NSCLC p with EGFR mutations. Methods: PIK3CA mutation status was assessed in pretreatment paraffin-embedded tumor samples from 118 advanced NSCLC p with EGFR mutations treated with erlotinib. E542K, E545K and H1047R mutations were screened by 5’-nuclease PCR (Taqman) assay and confirmed by standard PCR followed by sequencing. Results: PIK3CA mutations were detected in 6 of 118 patients (5.1%). 84% of p with PIK3CA mutations had adenocarcinomas vs 50% of p with wild-type (wt) PIK3CA (P=0.01). Response rate was 50% for p with mutations vs 70% for p with wt PIK3CA (P=0.03). There were no other differences between p with and without PIK3CA mutations. 2 of the 6 p with PIK3CA mutations had the uncommon L861Q mutation in exon 21 of EGFR. 1 of the 6 p had complete response; 2 had partial response; 3 had progressive disease. There was a non-significant trend towards shorter PFS for the 6 p with PIK3CA mutations (9 vs 16 m; P=0.59). MS was not reached for the 6 p with PIK3CA mutations, while it was 29 m for p with wt PIK3CA (P=0.09). Conclusions: PIK3CA mutations can be present in some EGFR-mutant NSCLC p, with lower response and a trend towards shorter PFS. Treatment with EGFR tyrosine kinase inhibitors plus PIK3CA inhibitors should be tested in this small subset of p with double mutations.