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

Harry H Yoon, N. R. Foster, J. P. Meyers, P. D. Steen, Daniel W Visscher, R. Pillai, D. M. Prow, C. M. Reynolds, B. T. Marchello, R. B. Mowat, B. I. Mattar, C. Erlichman, Matthew Philip Goetz

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15 Scopus citations

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/m2) 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.

Original languageEnglish (US)
Article numbermdv543
Pages (from-to)339-344
Number of pages6
JournalAnnals of Oncology
Volume27
Issue number2
DOIs
StatePublished - Feb 1 2016

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Keywords

  • Cancer of unknown primary
  • Everolimus
  • Expression profile
  • Platinum chemotherapy
  • Taxane chemotherapy
  • Tissue of origin

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

Yoon, H. H., Foster, N. R., Meyers, J. P., Steen, P. D., Visscher, D. W., Pillai, R., Prow, D. M., Reynolds, C. M., Marchello, B. T., Mowat, R. B., Mattar, B. I., Erlichman, C., & Goetz, M. P. (2016). Gene expression profiling identifies responsive patients with cancer of unknown primary treated with carboplatin, paclitaxel, and everolimus: NCCTG N0871 (alliance). Annals of Oncology, 27(2), 339-344. [mdv543]. https://doi.org/10.1093/annonc/mdv543