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Proffered Paper – Translational research

3562 - A phase 3 trial of empiric chemotherapy with cisplatin and gemcitabine or systemic treatment tailored by molecular gene expression analysis in patients with carcinomas of an unknown primary (CUP) site (GEFCAPI 04)


28 Sep 2019


Proffered Paper – Translational research


Tumour Site

Carcinoma of Unknown Primary Site (CUP)


Karim Fizazi


Annals of Oncology (2019) 30 (suppl_5): v851-v934. 10.1093/annonc/mdz394


K. Fizazi1, A. Maillard2, N. Penel3, G. Baciarello1, D. Allouache4, G. Daugaard5, A. Van de Wouw6, G. Soler7, E. Vauleon8, L. Chaigneau9, R. Jansen10, F. Losa Gaspa11, R. Morales Barrera12, C. Balana13, D. Tosi14, B. Chauffert15, C.A. Schnabel16, G. Martineau17, S. Culine18, I. Borget19

Author affiliations

  • 1 Cancer Medicine, Gustave Roussy, 94805 - Villejuif/FR
  • 2 Biostatistics, Gustave Roussy, 94805 - Villejuif/FR
  • 3 General Oncology Department, Centre Oscar Lambret, 59020 - Lille/FR
  • 4 Medical Oncology, Centre Francois Baclesse, Caen/FR
  • 5 Medical Oncology, Rigshospitalet, Copenhagen University Hospital, 2100 - Copenhagen/DK
  • 6 Medical Oncology, Medisch Centrum voor Noord-Limburg, Venlo/NL
  • 7 Medical Oncology, Institut Català d´Oncologia, Barcelona/ES
  • 8 Medical Oncology, Centre Eugene - Marquis, 35042 - Rennes/FR
  • 9 Medical Oncology, CHRU Jean Minjoz, Besançon/FR
  • 10 Medical Oncology, Maastricht University Medical Center, Maastricht/NL
  • 11 Medical Oncology, Hospital Moises Broggi, Barcelona/ES
  • 12 Medical Oncology Dept., Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 13 Medical Oncology, Germans Trias i Pujol, Barcelona/ES
  • 14 Medical Oncology, ICM Regional Cancer Institute of Montpellier, 34090 - Montpellier/FR
  • 15 Medical Oncology, CHU Amiens, Amiens-Picardie/FR
  • 16 Biology, bioTheranostics, Inc., San Diego/US
  • 17 Clinical Research, Institut Gustave Roussy, Villejuif/FR
  • 18 Medical Oncology, Hôpital Saint Louis, 75010 - Paris/FR
  • 19 Biostatistics, Institut Gustave Roussy, 94800 - Villejuif/FR


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Abstract 3562


CUP are heterogeneous tumors that share the unique characteristic of metastases with no identifiable origin. The outcome of patients (pts) with CUP is poor despite empiric chemotherapy that has activity against a wide variety of neoplasms such as the cisplatin-gemcitabine combination (Culine S, JCO 2002). Molecular tests may identify primary sites in up to 80% of pts, and results suggest that at least 1/3 of identified primaries may not be sensitive to empiric chemotherapy used in CUPs (Gross-Goupil G 2012). In the GEFCAPI 04 phase III trial, we hypothesized that tailored treatment will improve outcomes.


Eligible pts had pathologically-confirmed metastatic CUPs and were treatment naïve. Pts belonging to pre-defined favorable subsets were excluded. After relevant workup had identified no primary site, pts were randomized 1:1 to either Arm A (Cisplatin 100 mg/m² d1+ Gemcitabine 1250 mg/m², day 1 and 8, q3w) or Arm B (gene expression test followed by à la carte treatment according to the suspected primary). The test consisted of the Tissue Of Origin (Pathwork, n = 21) or CancerTYPE ID (Biotheranostics, n = 222). The primary endpoint was PFS (HR = 0.625, power=80%, 5% bilateral test). Stratification was on site, PS and LDH level. Secondary endpoints were PFS in pts with pre-defined cancers likely insensitive to cisplatin-gemcitabine and OS.


From 03/12 to 02/18, 243 pts from 4 EU countries were randomized (Arm A: 120, Arm B: 123). Primary cancers most often reported by tests were pancreatico-biliary cancer (19%), squamous cell carcinoma (11%, kidney cancer (8%), and lung cancer (8%). Treatment was tailored by molecular test results in 91/123 arm B pts (74%). PFS by central review was similar: HR = 0.95 (0.72-1.25); p = 0.7; medians: 5.3 m arm A vs 4.6 m arm B. PFS by local review also showed no significant difference: HR = 0.80 (0.60-1.06); p = 0.12; medians 5.8 vs 6.4 m. OS was also similar in the overall population (HR: 0.92 (0.69-1.23), medians: 10 vs 10.7 m) and in 60 pts with suspected cancers likely insensitive to GC.


In GEFCAPI 04, using a molecular test followed by tailored systemic treatment did not improve outcomes of pts with CUP.

Clinical trial identification


Editorial acknowledgement

Legal entity responsible for the study

Institut Gustave Roussy.


Programme Hospitalier de Recherche Clinique (PHRC) from the French Ministry of Health.


K. Fizazi: Advisory / Consultancy: Astellas; Advisory / Consultancy: AAA; Advisory / Consultancy: Bayer; Advisory / Consultancy: Clovis; Advisory / Consultancy: Curevac; Advisory / Consultancy: Incyte; Advisory / Consultancy: Janssen; Advisory / Consultancy: MSD; Advisory / Consultancy: Orion; Advisory / Consultancy: Sanofi. R. Morales Barrera: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Sanofi; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Astrazeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Asofarma; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Johnson and Jonhson; Honoraria (self), Advisory / Consultancy: Roche. C.A. Schnabel: Full / Part-time employment: bioTheranostics. All other authors have declared no conflicts of interest.

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