title: Relationship of Driver Oncogenes to Long-Term Pemetrexed Response in Non--Small-Cell Lung Cancer.
abstract: BACKGROUND
  Pemetrexed is approved in the treatment of advanced stage nonsquamous non-small-cell lung cancer (NSCLC). The length of response is variable, and we thus sought to identify which clinicopathologic characteristics are associated with long-term disease control with pemetrexed.
  
  
  METHODS
  Patients with metastatic NSCLC received pemetrexed (with or without bevacizumab) for 12 months or longer, either as maintenance treatment after first-line platinum-based chemotherapy or as subsequent treatment. Clinical and pathologic characteristics were collected.
  
  
  RESULTS
  Of a total of 196 patients who received pemetrexed starting in 2007, 25 patients were identified who received pemetrexed for over 1 year. Of these, 15 patients received pemetrexed with or without bevacizumab as maintenance treatment and 10 patients received pemetrexed as subsequent treatment. Fifteen (60%) of 25 patients had an oncogenic driver mutation as follows: 5 (20%) had ROS1 gene rearrangements, 4 (16%) had ALK gene rearrangements, 3 (12%) had KRAS mutations, 2 (8%) had epidermal growth factor receptor (EGFR) mutations, and 1 (4%) had an NRAS mutation. The median overall survival was 42.2 months (95% confidence interval, 37.4-61.3) and median progression-free survival was 22.1 months (95% confidence interval, 15.1-29.1). Patients with an oncogenic driver mutation had significantly better progression-free survival (P = .006) and overall survival (P = .001).
  
  
  CONCLUSIONS
  Among patients with NSCLC who received pemetrexed for an extended time, those with ALK and ROS1 gene rearrangements were proportionally overrepresented compared with that anticipated in a general nonsquamous NSCLC population, and patients with oncogenic driver mutations had improved outcomes.
authors: Department of Medical Oncology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; and Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
authors: Ying
authors: Y
authors: Liang
authors: Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA.
authors: Heather A
authors: HA
authors: Wakelee
authors: Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA. Electronic address: jwneal@stanford.edu.
authors: Joel W
authors: JW
authors: Neal
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D000068437:Pemetrexed / Q000008:administration & dosage / Q000627:therapeutic use*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D011518:Proto-Oncogene Proteins; D000068437:Pemetrexed; D000068258:Bevacizumab
keywords: Anaplastic lymphoma kinase (ALK); Driver oncogene; Epidermal growth factor receptor (EGFR); KRAS; NRAS; Non–small-cell lung cancer; Pemetrexed; ROS1