title: Multicenter, randomized, phase II trial of CI-1033, an irreversible pan-ERBB inhibitor, for previously treated advanced non small-cell lung cancer.
abstract: OBJECTIVE
  To evaluate the efficacy of the pan-ERBB inhibitor, CI-1033, in platinum-refractory or recurrent advanced-stage non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  This open-label, randomized phase II trial evaluated CI-1033 in patients with advanced-stage NSCLC who experienced treatment failure after or were refractory to platinum-based chemotherapy. Three oral CI-1033 doses were evaluated in 21-day dosing cycles: 50 mg daily for 21 consecutive days, 150 mg daily for 21 consecutive days, and 450 mg daily for 14 consecutive days followed by 7 days of no treatment. The primary efficacy end point was the 1-year survival rate.
  
  
  RESULTS
  One hundred sixty-six patients were randomly assigned to treatment. Baseline patient demographics were well balanced. The most common drug-related adverse events were rash and diarrhea. The 450-mg arm (14 days on/7 days off) was closed early due to an excessive rate of adverse events. The 1-year survival rates were 29%, 26%, and 29%, respectively, in the three arms. The response rates were 2%, 2%, and 4%, and stable disease was confirmed in 16%, 23%, and 18% of patients, respectively, in the three study arms. Exploratory analyses demonstrated a prolonged survival in patients who developed a rash and in those with baseline tumor ERBB-2 expression.
  
  
  CONCLUSIONS
  CI-1033 had modest activity in unselected NSCLC patients but did not meet its primary end point. Future studies should focus on identifying methods of patient selection.
authors.affiliation: Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA. pjanne@partners.org
authors.forename: Pasi A
authors.initials: PA
authors.lastname: Jänne
authors.forename: Joachim
authors.initials: J
authors.lastname: von Pawel
authors.forename: Roger B
authors.initials: RB
authors.lastname: Cohen
authors.forename: Lucio
authors.initials: L
authors.lastname: Crino
authors.forename: Charles A
authors.initials: CA
authors.lastname: Butts
authors.forename: Steven S
authors.initials: SS
authors.lastname: Olson
authors.forename: Irene A
authors.initials: IA
authors.lastname: Eiseman
authors.forename: Alberto A
authors.initials: AA
authors.lastname: Chiappori
authors.forename: Beow Y
authors.initials: BY
authors.lastname: Yeap
authors.forename: Peter F
authors.initials: PF
authors.lastname: Lenehan
authors.forename: Kathy
authors.initials: K
authors.lastname: Dasse
authors.forename: Meredith
authors.initials: M
authors.lastname: Sheeran
authors.forename: Philip D
authors.initials: PD
authors.lastname: Bonomi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D003967:Diarrhea / Q000139:chemically induced; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000009:adverse effects / Q000627:therapeutic use*; D015996:Survival Rate
chemical_list: D009025:Morpholines; C420268:Canertinib; C512478:EGFR protein, human; D066246:ErbB Receptors