title: TACTIC: a multicentre, open-label, single-arm phase II trial of panitumumab, cisplatin, and gemcitabine in biliary tract cancer.
abstract: OBJECTIVE
  The phase II TACTIC trial prospectively selected patients with KRAS wild-type advanced biliary tract cancer for first-line treatment with panitumumab and combination chemotherapy.
  
  
  METHODS
  Of 78 patients screened, 85 % had KRAS wild-type tumours and 48 were enrolled. Participants received cisplatin 25 mg/m(2) and gemcitabine 1000 mg/m(2) on day 1 and day 8 of each 21-day cycle and panitumumab 9 mg/kg on day 1 of each cycle. Treatment was continued until disease progression, unacceptable toxicity, or request to discontinue. The primary endpoint was the clinical benefit rate (CBR) at 12 weeks (complete response, partial response, or stable disease). CBR of 70 % was considered to be of clinical interest. Secondary outcomes were progression-free survival, time to treatment failure, overall survival, CA19.9 response and safety.
  
  
  RESULTS
  Thirty-four patients had a clinical benefit at 12 weeks, an actuarial rate of 80 % (95 % CI 65-89 %). 46 % had a complete or partial response. Median progression-free survival was 8.0 months (95 % CI 5.1-9.9) and median overall survival 11.9 months (95 % CI 7.4-15.8). Infection accounted for 27 % of the grade 3 or 4 toxicity, with rash (13 %), fatigue (13 %), and hypomagnesemia (10 %) among the more common grade 3 or 4 non-haematological toxicities.
  
  
  CONCLUSIONS
  A marker-driven approach to patient selection was feasible in advanced biliary tract cancer in an Australian population. The combination of panitumumab, gemcitabine, and cisplatin in KRAS wild-type cancers was generally well tolerated and showed promising clinical efficacy. Further exploration of anti-EGFR therapy in a more selected population is warranted.
authors.affiliation: National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia.|Department of Pathology, University of Melbourne, Parkville, VIC, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Ferraro
authors.affiliation: Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Goldstein
authors.affiliation: National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia.
authors.forename: R L
authors.initials: RL
authors.lastname: O'Connell
authors.affiliation: Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC, Australia.
authors.forename: J R
authors.initials: JR
authors.lastname: Zalcberg
authors.affiliation: National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia.
authors.forename: K M
authors.initials: KM
authors.lastname: Sjoquist
authors.affiliation: Austin Health, Melbourne, VIC, Australia.
authors.forename: N C
authors.initials: NC
authors.lastname: Tebbutt
authors.affiliation: Chris O'Brien Lifehouse, Sydney, NSW, Australia.
authors.forename: P
authors.initials: P
authors.lastname: Grimison
authors.affiliation: St Vincents Hospital, Melbourne, VIC, Australia.|University of Melbourne, Melbourne, VIC, Australia.
authors.forename: S
authors.initials: S
authors.lastname: McLachlan
authors.affiliation: Western Health, Melbourne, VIC, Australia.
authors.forename: L L
authors.initials: LL
authors.lastname: Lipton
authors.affiliation: Haematology and Oncology Clinics of Australasia, Wesley Medical Centre, Brisbane, QLD, Australia.
authors.forename: P
authors.initials: P
authors.lastname: Vasey
authors.affiliation: National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia.
authors.forename: V J
authors.initials: VJ
authors.lastname: Gebski
authors.affiliation: National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Aiken
authors.affiliation: Nambour General Hospital, Nambour, QLD, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Cronk
authors.affiliation: Sir Charles Gairdner Hospital, Nedlands, WA, Australia.
authors.forename: S
authors.initials: S
authors.lastname: Ng
authors.affiliation: Flinders University, Adelaide, SA, Australia.
authors.forename: C S
authors.initials: CS
authors.lastname: Karapetis
authors.affiliation: Department of Medical Oncology, Nepean Cancer Care Centre, PO Box 63, Penrith, Sydney, NSW, 2751, Australia. Jenny.Shannon@health.nsw.gov.au.
authors.forename: J
authors.initials: J
authors.lastname: Shannon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001315:Australia; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D018395:CA-19-9 Antigen / Q000097:blood; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077544:Panitumumab; D018579:Patient Selection; D011446:Prospective Studies; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000911:Antibodies, Monoclonal; D018395:CA-19-9 Antigen; C117307:KRAS protein, human; D003841:Deoxycytidine; D000077544:Panitumumab; D016283:Proto-Oncogene Proteins p21(ras); D002945:Cisplatin; D000093542:Gemcitabine
keywords: Biliary tract cancer; Cancer antigen 19.9; Chemotherapy; KRAS; Panitumumab; Phase II trial