title: Tumor marker analyses from the phase III, placebo-controlled, FASTACT-2 study of intercalated erlotinib with gemcitabine/platinum in the first-line treatment of advanced non-small-cell lung cancer.
abstract: The FASTACT-2 study of intercalated erlotinib with chemotherapy in Asian patients found that EGFR mutations were the main driver behind the significant progression-free survival (PFS) benefit noted in the overall population. Further exploratory biomarker analyses were conducted to provide additional insight.
  
  
  
  This multicenter, randomized, placebo-controlled, double-blind, phase III study investigated intercalated first-line erlotinib or placebo with gemcitabine/platinum, followed by maintenance erlotinib or placebo, for patients with stage IIIB/IV non-small cell lung cancer (NSCLC). Provision of samples for biomarker analysis was encouraged but not mandatory. The following biomarkers were analyzed (in order of priority): EGFR mutation by cobas(®) test, KRAS mutation by cobas(®)KRAS test, HER2 by immunohistochemistry (IHC), HER3 by IHC, ERCC1 by IHC, EGFR gene copy number by fluorescence in-situ hybridization (FISH) and EGFR by IHC. All subgroups were assessed for PFS (primary endpoint), overall survival (OS), non-progression rate and objective response rate.
  
  
  
  Overall, 256 patients provided samples for analysis. Considerable overlap was noted among biomarkers, except for EGFR and KRAS mutations, which are mutually exclusive. Other than EGFR mutations (p<0.0001), no other biomarkers were significantly predictive of outcomes in a treatment-by-biomarker interaction test, although ERCC1 IHC-positive status was predictive of improved OS for the erlotinib arm versus placebo in EGFR wild-type patients (median 18.4 vs 9.5 months; hazard ratio [HR] HR=0.32, 95% confidence intervals [CI]: 0.14-0.69, p=0.0024).
  
  
  
  Activating EGFR mutations were predictive for improved treatment outcomes with a first-line intercalated regimen of chemotherapy and erlotinib in NSCLC. ERCC1 status may have some predictive value in EGFR wild-type disease, but requires further investigation.
authors.affiliation: State Key Laboratory of Southern China, Department of Clinical Oncology, Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, China. Electronic address: tony@clo.cuhk.edu.hk.
authors.forename: Tony
authors.initials: T
authors.lastname: Mok
authors.affiliation: Lung Center of the Philippines, Quezon Ave., Diliman, Quezon City, Metro Manila, Philippines.
authors.forename: Guia
authors.initials: G
authors.lastname: Ladrera
authors.affiliation: Siriraj Hospital, 2 Wanglang Road, Bangkok, Bangkoknoi 10700, Thailand.
authors.forename: Vichien
authors.initials: V
authors.lastname: Srimuninnimit
authors.affiliation: King Chulalongkorn Memorial Hospital, 1873 Rama 4 Road, Bangkok, Pathumwan 10330, Thailand.
authors.forename: Virote
authors.initials: V
authors.lastname: Sriuranpong
authors.affiliation: National Taiwan University Hospital, No. 7, Zhongshan S Rd., Zhongzheng District, Taipei, Taiwan.
authors.forename: Chong-Jen
authors.initials: CJ
authors.lastname: Yu
authors.affiliation: Faculty of Medicine, Chiangmai University, Chiang Mai, Thailand.
authors.forename: Sumitra
authors.initials: S
authors.lastname: Thongprasert
authors.affiliation: Philippine General Hospital, Taft Avenue Ermita, Brgy 670 Zone 72, Manila, 1000 Metro Manila, Philippines.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Sandoval-Tan
authors.affiliation: National Cancer Center, Goyang, Republic of Korea.
authors.forename: Jin Soo
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Rizal Medical Center, Pasig Blvd, Pasig, Metro Manila, Philippines.
authors.forename: Fatima
authors.initials: F
authors.lastname: Fuerte
authors.affiliation: Oncology Biomarker Development, Genentech Inc., South San Francisco, CA 94080, United States.
authors.forename: David S
authors.initials: DS
authors.lastname: Shames
authors.affiliation: F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Klughammer
authors.affiliation: F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: Matt
authors.initials: M
authors.lastname: Truman
authors.affiliation: F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: Pablo
authors.initials: P
authors.lastname: Perez-Moreno
authors.affiliation: Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China. Electronic address: syylwu@live.cn.
authors.forename: Yi-Long
authors.initials: YL
authors.lastname: Wu
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D009367:Neoplasm Staging; D010984:Platinum / Q000008:administration & dosage; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D014408:Biomarkers, Tumor; D003841:Deoxycytidine; D010984:Platinum; D000069347:Erlotinib Hydrochloride; D000093542:Gemcitabine
keywords: Biomarkers; EGFR; Erlotinib; NSCLC