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Clinical Trial
. 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)

H H Yoon  1 , N R Foster  2 , J P Meyers  2 , P D Steen  3 , D W Visscher  4 , R Pillai  5 , D M Prow  6 , C M Reynolds  7 , B T Marchello  8 , R B Mowat  9 , B I Mattar  10 , C Erlichman  1 , M P Goetz  11
Affiliations
Clinical Trial

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

H H Yoon et al. Ann Oncol. 2016 Feb.

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.

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Figures

Figure 1.
Figure 1.
Tumor response rates (A), overall survival (B), and progression-free survival (C) in patients with metastatic carcinoma of unknown primary treated with everolimus, carboplatin, and paclitaxel therapy in the N0871/Alliance trial are shown, according to whether gene expression analysis predicted a platinum/taxane-sensitive v-resistant tumor profile. aExcludes one case where tumor response was not assessed.
See this image and copyright information in PMC

References

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