title: Changes in 18F-fluorodeoxyglucose and 18F-fluorodeoxythymidine positron emission tomography imaging in patients with non-small cell lung cancer treated with erlotinib.
abstract: OBJECTIVE
  Assessing clinical activity of molecularly targeted anticancer agents, especially in the absence of tumor shrinkage, is challenging. To evaluate on-treatment 18F-fluorodeoxyglucose (FDG) and/or 18F-fluorodeoxythymidine (FLT) positron emission tomography (PET) for this purpose, we conducted a prospective multicenter trial assessing PET response rates and associations with progression-free (PFS) and overall survival (OS) in 2nd/3rd-line non-small-cell lung cancer patients treated with erlotinib.
  
  
  METHODS
  PET/computed tomography (CT) scans were conducted at baseline, day (d)14 and d56 after the first daily erlotinib dose, with diagnostic CT at baseline and d56 (all scans centrally reviewed). PET partial metabolic response (PMR) was defined as a mean decrease (in ≤ 5 lesions/patient) of 15% or more maximum standardized uptake value. PFS was investigator-determined.
  
  
  RESULTS
  Of 74 erlotinib-treated patients, 51 completed all imaging assessments through d56; 13 of 51 (26%) FDG-evaluable patients had PMR at d14, as did 9 of 50 (18%) FLT-evaluable patients. Four (7.8%) showed partial responses (PR) by d56 CT; all 4 had PMR by d14 FDG-PET with 3 PMRs by d14 FLT-PET. Three of the 4 patients with CT PR had evaluable archival tumor tissue; all 3 had epidermal growth factor receptor mutations. D14 and d56 PMRs by FDG or FLT were associated with improved PFS; HRs for PET responders versus nonresponders were 0.3 to 0.4. D14 FDG-PET PMR was associated with improved OS (P = 0.03) compared with FDG-PET nonresponders.
  
  
  CONCLUSIONS
  Early (d14) FDG-PET PMR is associated with improved PFS and OS, even in the absence of subsequent Response Evaluation Criteria in Solid Tumors response. These data support inclusion of FDG-PET imaging in clinical trials testing novel targeted therapies, particularly those with anticipated cytostatic effects.
authors.affiliation: Peter MacCallum Cancer Centre, East Melbourne, The University of Melbourne, Parkville, Australia. linda.mileshkin@petermac.org
authors.forename: Linda
authors.initials: L
authors.lastname: Mileshkin
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Hicks
authors.forename: Brett G M
authors.initials: BG
authors.lastname: Hughes
authors.forename: Paul L R
authors.initials: PL
authors.lastname: Mitchell
authors.forename: Veena
authors.initials: V
authors.lastname: Charu
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Gitlitz
authors.forename: David
authors.initials: D
authors.lastname: Macfarlane
authors.forename: Benjamin
authors.initials: B
authors.lastname: Solomon
authors.forename: Lukas C
authors.initials: LC
authors.lastname: Amler
authors.forename: Wei
authors.initials: W
authors.lastname: Yu
authors.forename: Andrea
authors.initials: A
authors.lastname: Pirzkall
authors.forename: Bernard M
authors.initials: BM
authors.lastname: Fine
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D000069347:Erlotinib Hydrochloride; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging / Q000379:methods; D049268:Positron-Emission Tomography / Q000379:methods; D011799:Quinazolines / Q000627:therapeutic use*; D019275:Radiopharmaceuticals; D016019:Survival Analysis; D013936:Thymidine / Q000031:analogs & derivatives*
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D000069347:Erlotinib Hydrochloride; D013936:Thymidine