title: Customized adjuvant phase II trial in patients with non-small-cell lung cancer: IFCT-0801 TASTE.
abstract: OBJECTIVE
  Surgical resection plus adjuvant platinum-based chemotherapy is considered standard care for stage II to III non-small-cell lung cancer (NSCLC), but its efficacy is limited, and it involves toxic risks, justifying patient-tailored treatment. Excision repair cross-complementation group 1 (ERCC1) was shown to predict cisplatin-based chemotherapy response; EGFR mutations were predictive of epidermal growth factor receptor inhibition response.
  
  
  METHODS
  This prospective randomized phase II trial enrolled 150 patients with completely resected non-squamous cell stage II or IIIA (non-N2) tumors. Patients in the control arm (n = 74) were treated with four standard-dose courses of cisplatin plus pemetrexed (CP). In the customized treatment arm (n = 76), patients with activated EGFR mutations received erlotinib 150 mg for 1 year; ERCC1-negative patients received four CP courses, whereas ERCC1-positive patients underwent follow-up. The trial sought to demonstrate the feasibility of customized adjuvant chemotherapy based on timely biomarker analysis within a 2-month postsurgery delay. Secondary objectives were tolerability, compliance with adjuvant therapy, and biomarker distribution.
  
  
  RESULTS
  In arm A, all patients received CP; in arm B, seven received erlotinib, 53 were administered CP, and 16 underwent follow-up. Median erlotinib exposure was 344 days. Of the 127 patients allocated to CP, 82% received four cycles with good tolerability. The overall success rate of the trial (ie, percentage of patients with complete biomarker status able to start adjuvant treatment within 2 months of surgery) was 80%.
  
  
  CONCLUSIONS
  The primary end point of the trial was met, demonstrating the feasibility of a national biology-driven trial in the adjuvant NSCLC setting. Nevertheless, the phase III part was canceled because of the unreliability of the ERCC1 immunohistochemical readouts.
authors.affiliation: Marie Wislez and Jacques Cadranel, Hôpital Tenon, Assistance Publique des Hôpitaux de Paris; Franck Morin, Intergroupe Francophone de Cancérologie Thoracique, Paris; Fabrice Barlesi, Aix Marseille University, Assistance Publique des Hôpitaux de Marseille; Anne Madroszyck, Institut Paoli Calmettes, Marseille; Benjamin Besse and Jean-Charles Soria, Institut Gustave Roussy, Villejuif; Julien Mazières, Hôpital Larrey, Toulouse; Patrick Merle, Centre Hospitalier Universitaire (CHU) de Clermont-Ferrand, Clermont-Ferrand; Clarisse Audigier-Valette, Hôpital Sainte Musse, Toulon; Denis Moro-Sibilot, CHU de Grenoble, Grenoble; Laure Gautier-Felizot, Centre Hospitalier de Dax, Dax; François Goupil, Centre Hospitalier du Mans, Le Mans; Aldo Renault, Centre Hospitalier de Pau, Pau; Elisabeth Quoix, Nouvel Hôpital Strasbourg, Strasbourg; Pierre-Jean Souquet, Centre Hospitalier Lyon-Sud; David Pérol, Centre Léon Bérard, Lyon; Romain Corre, Hôpital Pontchaillou, Rennes; and Gérard Zalcman, CHU Caen, Caen, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Wislez
authors.forename: Fabrice
authors.initials: F
authors.lastname: Barlesi
authors.forename: Benjamin
authors.initials: B
authors.lastname: Besse
authors.forename: Julien
authors.initials: J
authors.lastname: Mazières
authors.forename: Patrick
authors.initials: P
authors.lastname: Merle
authors.forename: Jacques
authors.initials: J
authors.lastname: Cadranel
authors.forename: Clarisse
authors.initials: C
authors.lastname: Audigier-Valette
authors.forename: Denis
authors.initials: D
authors.lastname: Moro-Sibilot
authors.forename: Laure
authors.initials: L
authors.lastname: Gautier-Felizot
authors.forename: François
authors.initials: F
authors.lastname: Goupil
authors.forename: Aldo
authors.initials: A
authors.lastname: Renault
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Quoix
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Souquet
authors.forename: Anne
authors.initials: A
authors.lastname: Madroszyck
authors.forename: Romain
authors.initials: R
authors.lastname: Corre
authors.forename: David
authors.initials: D
authors.lastname: Pérol
authors.forename: Franck
authors.initials: F
authors.lastname: Morin
authors.forename: Gérard
authors.initials: G
authors.lastname: Zalcman
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000378:metabolism; D004720:Endonucleases / Q000378:metabolism; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D000068437:Pemetrexed; D011446:Prospective Studies
chemical_list: D004268:DNA-Binding Proteins; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin