Association between efficacy of pemetrexed and EGFR mutation status for EGFR mutated lung carcinoma

Background: Subgroup analysis of Japanese patients in a LUX-Lung 3 trial showed different progression-free survival (PFS) after cisplatin (CDDP) plus pemetrexed (PEM) treatment between patients in the exon 21 L858R (L858R) group (8.3 months) and the exon 19 deletion (19 del) group (3.1 months). PEM may have different efficacies in patients with L858R or 19 del. Methods: Consecutive patients with advanced/recurrent non-small cell lung cancer (NSCLC) harboring activating EGFR mutations were treated with platinum combined with PEM at our institute. The primary endpoint was to compare PFS of L858R patients to that of 19 del patients, among all patients with EGFR-mutated NSCLC. Results: Thirty-two patients treated between 2009 and 2013 were included. The median age was 67 years (range: 40-78 years). Thirteen patients (41%) had L858R and 19 patients (59%) had 19 del. Patients were treated with CDDP (n = 5) or carboplatin (n=27) combined with PEM. Compared with the 19 del group, the L858R group included more female patients (64% versus 47%, p=0.002), fewer patients treated with CDDP(8% versus 21%, p=0.018), and more patients with PEM maintenance therapy (50% versus 29%, p=0.003). The median number of cycles of platinum combined with PEM was 4 (range: 1-6), and 13 patients received maintenance therapy. The response rate (RR) was 33.3% among L858R and 22.2% among 19 del (p=0.65l). The median PFS was 5.13 months for L858R and 5.40 months for 19 del (p=0.824, HR=1.098, 95% CI: 0.48-2.50). The median overall survival (OS) was 29.17 months for L858R and 32.60 months for 19 del (p=0.232, HR=1.75, 95%CI: 0.69-4.45). Conclusions: This study did not show that PFS after platinum combined with PEM of L858R was superior to that of 19 del. RR and OS were consistent with PFS. A prospective trial is warranted to confirm the results of this study.