title: Pemetrexed-based chemotherapy in advanced lung adenocarcinoma patients with different EGFR genotypes.
abstract: Advanced lung adenocarcinoma patients with epidermal growth factor receptor (EGFR) activating mutations usually are highly sensitive to EGFR tyrosine kinase inhibitors (TKIs), but whether EGFR-mutant lung adenocarcinoma is also responsive to pemetrexed-based chemotherapy remains controversial. We conducted a retrospective study to evaluate the efficacy and outcome of pemetrexed-based chemotherapy in advanced lung adenocarcinoma patients with different EGFR mutation statuses. Sixty-nine EGFR-mutant and 89 wild-type patients with advanced lung adenocarcinoma were enrolled. They all had received pemetrexed-based treatments. Chemotherapy objective response rate (ORR), median progression-free survival (mPFS), and thymidylate synthase (TS) expression levels of EGFR-mutant patients were compared with those of EGFR-wild-type patients. For the EGFR-mutant patients treated with first-line platinum/pemetrexed combinations, the ORR was significantly higher than that of the wild-type patients treated with similar regimens (43 vs. 21%, p = 0.039). Nonetheless, for the patients treated with pemetrexed monotherapy, the difference in ORR was not significant between patients with EGFR mutations and those with wild-type EGFR in any line of treatments (in the first-line setting 20 vs. 13%, p = 0.715; in the second-/third-line setting 13 vs. 8%, p = 0.655). On the other hand, the mPFS for the EGFR-mutant patients treated with first-line combinations was also obviously prolonged (8.3 vs. 6.7 months, p = 0.004). However, among the patients receiving second-line platinum/pemetrexed combinations or any line of single-agent pemetrexed, there was no difference in PFS between EGFR-mutant and wild-type patients. Our results indicated that the efficacies and outcomes of pemetrexed treatment in advanced lung adenocarcinoma patients with EGFR activating mutations were similar to those in patients with EGFR-wild-type genotype, except in the setting of first-line platinum/pemetrexed combination chemotherapy.
authors.affiliation: Department of Thoracic Medical Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.
authors.forename: Xiangli
authors.initials: X
authors.lastname: Jiang
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Jiuqin
authors.initials: J
authors.lastname: Lu
authors.forename: Zhongli
authors.initials: Z
authors.lastname: Zhan
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.forename: Xiubao
authors.initials: X
authors.lastname: Ren
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005838:Genotype; D005971:Glutamates / Q000008:administration & dosage*; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000068437:Pemetrexed; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D013940:Thymidylate Synthase
chemical_list: D005971:Glutamates; D047428:Protein Kinase Inhibitors; D000068437:Pemetrexed; D006147:Guanine; D013940:Thymidylate Synthase; C512478:EGFR protein, human; D066246:ErbB Receptors