title: Pemetrexed-based chemotherapy in patients with advanced, ALK-positive non-small cell lung cancer.
abstract: BACKGROUND
  Anaplastic lymphoma kinase (ALK)-positive non-small-cell lung cancer (NSCLC) is highly responsive to crizotinib. To determine whether ALK-positive NSCLC is also sensitive to pemetrexed, we retrospectively evaluated progression-free survival (PFS) of ALK-positive versus ALK-negative patients who had been treated with pemetrexed-based chemotherapy for advanced NSCLC.
  
  
  METHODS
  We identified 121 patients with advanced, ALK-positive NSCLC in the USA, Australia, and Italy. For comparison, we evaluated 266 patients with advanced, ALK-negative, epidermal growth factor receptor (EGFR)-wild-type NSCLC, including 79 with KRAS mutations and 187 with wild-type KRAS (WT/WT/WT). We determined PFS on different pemetrexed regimens.
  
  
  RESULTS
  Among 70 ALK-positive patients treated with a platinum/pemetrexed regimen, the median PFS (mPFS) was 7.3 months (95% confidence interval (CI) 5.5-9.5). The mPFS of 51 ALK-positive patients treated with single-agent pemetrexed or nonplatinum/pemetrexed combinations was 5.5 months (2.8-9.0). For ALK-negative patients, PFS on all pemetrexed-based regimens was similar to that of ALK-positive patients, except in the specific setting of first-line platinum/pemetrexed where the mPFS was only 4.2 and 5.4 months in KRAS and WT/WT/WT patients, respectively. However, among patients with a never/light-smoking history (0-10 pack-year smoking history) treated with first-line platinum/pemetrexed, there was no difference in PFS between ALK-positive and ALK-negative patients.
  
  
  CONCLUSIONS
  PFS on pemetrexed or nonplatinum/pemetrexed combinations was similar in ALK-positive and ALK-negative patients. PFS on first-line platinum/pemetrexed may be prolonged in never/light-smoking patients regardless of ALK status.
authors.affiliation: Department of Medicine Hematology/Oncology, Massachusetts General Hospital Cancer Center, Boston, MA 02114, USA. ashaw1@partners.org
authors.forename: A T
authors.initials: AT
authors.lastname: Shaw
authors.forename: A M
authors.initials: AM
authors.lastname: Varghese
authors.forename: B J
authors.initials: BJ
authors.lastname: Solomon
authors.forename: D B
authors.initials: DB
authors.lastname: Costa
authors.forename: S
authors.initials: S
authors.lastname: Novello
authors.forename: M
authors.initials: M
authors.lastname: Mino-Kenudson
authors.forename: M M
authors.initials: MM
authors.lastname: Awad
authors.forename: J A
authors.initials: JA
authors.lastname: Engelman
authors.forename: G J
authors.initials: GJ
authors.lastname: Riely
authors.forename: V
authors.initials: V
authors.lastname: Monica
authors.forename: B Y
authors.initials: BY
authors.lastname: Yeap
authors.forename: G V
authors.initials: GV
authors.lastname: Scagliotti
mesh_terms: D000328:Adult; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology; D005260:Female; D005971:Glutamates / Q000627:therapeutic use*; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D013940:Thymidylate Synthase / Q000378:metabolism; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D013940:Thymidylate Synthase; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases