Is Pemetrexed Effective for the Activating EGFR Mutation-Positive Non-Squamous Non-Small-Cell Cancer?

ABSTRACT Background Pemetrexed (PEM) is the multitargeted antifolate chemotherapy agent and effective for non-squamous non-small-cell lung cancer (NSCLC). These tumors sometimes harbor the epidermal growth factor receptor (EGFR) activating mutation. We investigated the effectiveness of PEM for the EGFR activating mutation-positive NSCLC (EGFR-mt NSCLC). Patients and methods Between May 2009 and Jan 2012, a total of 36 patients were treated with PEM alone or PEM containing regimen. We retrospectively analyzed these patients. Results The number of male/female was 12/24 and the median age (range) was 64 (44–81); histology was all adenocarcinoma; EGFR mutation pattern exon 18/19/21, 2/20/14; stage IV/recurrence (including chemoradiotherapy recurrence), 28/8; smoking status never/former/current, 24/10/2; ECOG PS 0/1/2/3, 11/20/4/1. Eight patients did not receive the EGFR tyrosine kinase inhibitor before PEM treatment. Thirteen patients were treated with PEM–platinum combination chemotherapy as the cytotoxic agent first-line setting. One patient was treated with the PEM, carboplatin and bevacizumab (BEV) in the second-line setting. Eighteen patients were treated with PEM alone (10 patients were treated with PEM as the cytotoxic agent second-line setting). Four patients were with PEM + BEV. Six of 13 patients who received the PEM–platinum combination chemotherapy as the cytotoxic agent first-line setting achieved the objective response and the objective response rate (ORR) was 46%. Progression-free survival (PFS) was 7.4 months in this population. In the other hands, none of 10 patients who received the PEM alone as the cytotoxic agent second-line setting achieved the objective response and ORR was 0%. PFS was 1.6 months. Conclusions The PEM–platinum regimen is effective for the EGFR-mt NSCLC in the cytotoxic agent first-line setting. However, PEM alone might not be active for the EGFR-mt NSCLC in the cytotoxic agent second-line setting.