EGFR mutation and response to chemotherapy in non-small-cell lung cancer (NSCLC) patients

Abstract

7084 Background: EGFR mutation is associated with response and prolonged survival in NSCLC patients treated with gefitinib. However, its relevance in terms of response to conventional chemotherapeutics has not been investigated. We have retrospectively analyzed response to prior chemotherapies in NSCLC patients treated with gefitinib. Methods: EGFR mutation (mt) in exons 18, 19, 21, and 23 were identified by direct sequencing of PCR products of DNA extracted from archival paraffin embedded tissue. P-Erk (E) and p-Akt (A) expression was determined by immunohistochemistry. Response rate (RR) and time-to-progression (TTP) of prior chemotherapies of paclitaxel, platinum, and gemcitabine were analyzed in respect to EGFR mt and E and A expression. Results: 38 patients received paclitaxel in 1st-line chemotherapy (CRx). RR was not affected by EGFR mt (50% in mt(+) vs. 47% in mt(-), p=0.59), E (44% in E(+) vs. 45% in E(-), p=0.61) or A (46% in A(-/+) vs. 50% in A(2+), p=0.55). TTP was not affected by EGFR mt, E, or A. 54 patients received platinum in 1st-line CRx. RR was not affected by EGFR mt (50% in mt(+) vs. 37% in mt(-), p=0.59), E (37% in E(+) vs. 36% in E(-), p=0.60) or A (38% in A(-/+) vs. 41% in A(2+), p=0.52). TTP was not affected by EGFR mt, E, or A. 50 patients received gemcitabine in 1st- or 2nd-line CRx. RR was not affected by EGFR mt (25% in mt(+) vs. 18% in mt(-), p=.69), or A (19% in A(-/+) vs. 21% in A(2+), p=1.00). TTP was not affected by EGFR mt, E, or A. Of note, all responders to gemcitabine exhibited (+) E expression (RR 29% in E(+) vs. 0% in E(-), p=0.044). Conclusions: EGFR mutation was not associated with response to chemotherapies which included paclitaxel, platinum, or gemcitabine. These results support the use of gefitinib prior to other chemotherapeutics in patients with EGFR mutation. In addition, our results suggest the possibility that gefitinib resistant E (+) patients may benefit from gemcitabine. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca