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Ann Oncol. 2016 Feb;27(2):339-44. doi: 10.1093/annonc/mdv543. Epub 2015 Nov 16.

Gene expression profiling identifies responsive patients with cancer of unknown primary treated with carboplatin, paclitaxel, and everolimus: NCCTG N0871 (alliance).

Author information

1
Division of Medical Oncology.
2
Alliance Statistics and Data Center, Mayo Clinic, Rochester.
3
Department of Medical Oncology, Meritcare Hospital CCOP, Fargo.
4
Department of Anatomic Pathology, Mayo Clinic, Rochester.
5
Pathwork Diagnostics, Redwood City.
6
Department of Medical Oncology, Iowa Oncology Research Association CCOP, Des Moines.
7
Department of Hematology/Medical Oncology, Michigan Cancer Research Consortium, Ann Arbor.
8
Department of Medical Oncology, Montana Cancer Consortium, Billings.
9
Department of Medical Oncology/Hematology, Toledo Community Hospital Oncology Program CCOP, Toledo.
10
Department of Medical Oncology/Hematology, Wichita Community Clinical Oncology Program, Wichita, USA.
11
Division of Medical Oncology goetz.matthew@mayo.edu.

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.

PATIENTS AND 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.

CLINICALTRIALSGOV:

NCT00936702.

KEYWORDS:

cancer of unknown primary; everolimus; expression profile; platinum chemotherapy; taxane chemotherapy; tissue of origin

PMID:
26578722
PMCID:
PMC4907341
DOI:
10.1093/annonc/mdv543
[Indexed for MEDLINE]
Free PMC Article

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