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

Research output: Contribution to journalArticle

12 Citations (Scopus)

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

Fingerprint

Carboplatin
Gene Expression Profiling
Paclitaxel
Neoplasms
Carcinoma
Platinum
Everolimus
Tumor Biomarkers
Area Under Curve
Confidence Intervals
Biopsy
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

Gene expression profiling identifies responsive patients with cancer of unknown primary treated with carboplatin, paclitaxel, and everolimus : NCCTG N0871 (alliance). / Yoon, Harry H; Foster, N. R.; Meyers, J. P.; Steen, P. D.; Visscher, Daniel W; Pillai, R.; Prow, D. M.; Reynolds, C. M.; Marchello, B. T.; Mowat, R. B.; Mattar, B. I.; Erlichman, C.; Goetz, Matthew Philip.

In: Annals of Oncology, Vol. 27, No. 2, mdv543, 01.02.2016, p. 339-344.

Research output: Contribution to journalArticle

Yoon, HH, Foster, NR, Meyers, JP, Steen, PD, Visscher, DW, Pillai, R, Prow, DM, Reynolds, CM, Marchello, BT, Mowat, RB, Mattar, BI, Erlichman, C & Goetz, MP 2016, 'Gene expression profiling identifies responsive patients with cancer of unknown primary treated with carboplatin, paclitaxel, and everolimus: NCCTG N0871 (alliance)', Annals of Oncology, vol. 27, no. 2, mdv543, pp. 339-344. https://doi.org/10.1093/annonc/mdv543
Yoon, Harry H ; Foster, N. R. ; Meyers, J. P. ; Steen, P. D. ; Visscher, Daniel W ; Pillai, R. ; Prow, D. M. ; Reynolds, C. M. ; Marchello, B. T. ; Mowat, R. B. ; Mattar, B. I. ; Erlichman, C. ; Goetz, Matthew Philip. / Gene expression profiling identifies responsive patients with cancer of unknown primary treated with carboplatin, paclitaxel, and everolimus : NCCTG N0871 (alliance). In: Annals of Oncology. 2016 ; Vol. 27, No. 2. pp. 339-344.
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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.",
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AU - Yoon, Harry H

AU - Foster, N. R.

AU - Meyers, J. P.

AU - Steen, P. D.

AU - Visscher, Daniel W

AU - Pillai, R.

AU - Prow, D. M.

AU - Reynolds, C. M.

AU - Marchello, B. T.

AU - Mowat, R. B.

AU - Mattar, B. I.

AU - Erlichman, C.

AU - Goetz, Matthew Philip

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N2 - 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.

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KW - Tissue of origin

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