title: Gene expression profiling identifies responsive patients with cancer of unknown primary treated with carboplatin, paclitaxel, and everolimus: NCCTG N0871 (alliance).
abstract: BACKGROUND
  Carboplatin (C) and paclitaxel (P) are standard treatments for carcinoma of unknown primary (CUP). Everolimus, an mTOR inhibitor, exhibits activity in diverse cancer types. We did a phase II trial combining everolimus with CP for CUP. We also evaluated whether a gene expression profiling (GEP) test that predicts tissue of origin (TOO) could identify responsive patients.
  
  
  METHODS
  A tumor biopsy was required for central confirmation of CUP and GEP. Patients with metastatic, untreated CUP received everolimus (30 mg weekly) with P (200 mg/m(2)) and C (area under the curve 6) every 3 weeks. The primary end point was response rate (RR), with 22% needed for success. The GEP test categorized patients into two groups: those having a TOO where CP is versus is not considered standard therapy.
  
  
  RESULTS
  Of 45 assessable patients, the RR was 36% (95% confidence interval 22% to 51%), which met criteria for success. Grade ≥3 toxicities were predominantly hematologic (80%). Adequate tissue for GEP was available in 38 patients and predicted 10 different TOOs. Patients with a TOO where platinum/taxane is a standard (n = 19) tended to have higher RR (53% versus 26%) and significantly longer PFS (6.4 versus 3.5 months) and OS (17.8 versus 8.3 months, P = 0.005), compared with patients (n = 19) with a TOO where platinum/taxane is not standard.
  
  
  CONCLUSIONS
  Everolimus combined with CP demonstrated promising antitumor activity and an acceptable side-effect profile. A tumor biomarker identifying TOO may be useful to select CUP patients for specific antitumor regimens.
  
  
  BACKGROUND
  NCT00936702.
authors.affiliation: Division of Medical Oncology.
authors.forename: H H
authors.initials: HH
authors.lastname: Yoon
authors.affiliation: Alliance Statistics and Data Center, Mayo Clinic, Rochester.
authors.forename: N R
authors.initials: NR
authors.lastname: Foster
authors.affiliation: Alliance Statistics and Data Center, Mayo Clinic, Rochester.
authors.forename: J P
authors.initials: JP
authors.lastname: Meyers
authors.affiliation: Department of Medical Oncology, Meritcare Hospital CCOP, Fargo.
authors.forename: P D
authors.initials: PD
authors.lastname: Steen
authors.affiliation: Department of Anatomic Pathology, Mayo Clinic, Rochester.
authors.forename: D W
authors.initials: DW
authors.lastname: Visscher
authors.affiliation: Pathwork Diagnostics, Redwood City.
authors.forename: R
authors.initials: R
authors.lastname: Pillai
authors.affiliation: Department of Medical Oncology, Iowa Oncology Research Association CCOP, Des Moines.
authors.forename: D M
authors.initials: DM
authors.lastname: Prow
authors.affiliation: Department of Hematology/Medical Oncology, Michigan Cancer Research Consortium, Ann Arbor.
authors.forename: C M
authors.initials: CM
authors.lastname: Reynolds
authors.affiliation: Department of Medical Oncology, Montana Cancer Consortium, Billings.
authors.forename: B T
authors.initials: BT
authors.lastname: Marchello
authors.affiliation: Department of Medical Oncology/Hematology, Toledo Community Hospital Oncology Program CCOP, Toledo.
authors.forename: R B
authors.initials: RB
authors.lastname: Mowat
authors.affiliation: Department of Medical Oncology/Hematology, Wichita Community Clinical Oncology Program, Wichita, USA.
authors.forename: B I
authors.initials: BI
authors.lastname: Mattar
authors.affiliation: Division of Medical Oncology.
authors.forename: C
authors.initials: C
authors.lastname: Erlichman
authors.affiliation: Division of Medical Oncology goetz.matthew@mayo.edu.
authors.forename: M P
authors.initials: MP
authors.lastname: Goetz
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000627:therapeutic use*; D018572:Disease-Free Survival; D000068338:Everolimus / Q000627:therapeutic use*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D017239:Paclitaxel / Q000627:therapeutic use*; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000068338:Everolimus; D016190:Carboplatin; D017239:Paclitaxel
keywords: cancer of unknown primary; everolimus; expression profile; platinum chemotherapy; taxane chemotherapy; tissue of origin