Randomized Phase II Trial Comparing Site-Specific Treatment Based on Gene Expression Profiling With Carboplatin and Paclitaxel for Patients With Cancer of Unknown Primary Site

2019 ◽  
Vol 37 (7) ◽  
pp. 570-579 ◽  
Author(s):  
Hidetoshi Hayashi ◽  
Takayasu Kurata ◽  
Yuichi Takiguchi ◽  
Makoto Arai ◽  
Koji Takeda ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Specific Treatment ◽  
Progression Free Survival ◽  
Unknown Primary ◽  
Specific Therapy ◽  
Site Specific ◽  
Patients With Cancer ◽  
Empirical Chemotherapy

PURPOSE Although gene expression profiling is a promising diagnostic technique to determine the tissue of origin for patients with cancer of unknown primary site (CUP), no clinical trial has evaluated yet site-specific therapy directed by this approach compared with empirical chemotherapy. We therefore performed a randomized study to assess whether such site-specific therapy improves outcome compared with empirical chemotherapy in previously untreated patients with CUP. PATIENTS AND METHODS Comprehensive gene expression profiling was performed by microarray analysis, and an established algorithm was applied to predict tumor origin. Patients with CUP were randomly assigned (1:1) to receive standard site-specific therapy or empirical paclitaxel and carboplatin (PC). The primary end point was 1-year survival rate. RESULTS One hundred thirty patients were randomly assigned and had sufficient biopsy tissue for molecular analysis. Efficacy analysis was performed for 50 and 51 patients in the site-specific therapy and empirical PC arms, respectively. Cancer types most commonly predicted were pancreatic (21%), gastric (21%), and lymphoma (20%). The 1-year survival rate was 44.0% and 54.9% for site-specific treatment and empirical PC ( P = .264), respectively. Median overall and progression-free survival were 9.8 and 5.1 months, respectively, for site-specific treatment versus 12.5 and 4.8 months for empirical PC ( P = .896 and .550, respectively). Median overall survival (16.7 v 10.6 months; P = .116) and progression-free survival (5.5 v 3.9 months; P = .018) were better for predicted more-responsive than less-responsive tumor types. CONCLUSION Site-specific treatment that was based on microarray profiling did not result in a significant improvement in 1-year survival compared with empirical PC, although prediction of the original site seemed to be of prognostic value.

Use of gene expression profiling to identify responsive patients treated with carboplatin (Carb), paclitaxel (Pac), and everolimus as first-line treatment for cancer of unknown primary (CUP): NCCTG N0871 (Alliance).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2562-2562
Author(s):  
Matthew P. Goetz ◽  
Nathan R. Foster ◽  
Jeffery P. Meyers ◽  
Preston D. Steen ◽  
Daniel W. Visscher ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Progression Free Survival ◽  
Unknown Primary ◽  
First Line ◽  
First Line Therapy ◽  
Secondary Endpoints ◽  
Tissue Of Origin ◽  
Central Pathology

2562 Background: Empiric chemotherapy (taxane/platinum) is standard for CUP. Because prognosis is poor, novel approaches are needed. The PI3K/mTOR pathway is frequently dysregulated in cancer. Everolimus (E), an mTOR inhibitor, is approved for multiple malignancies. We performed a phase II study of Pac + Carb + E as first-line therapy in metastatic CUP patients (pts). We additionally determined if a gene expression profiling (GEP) test that identifies tissue of origin (Pathwork Tissue of Origin) could identify responsive pts. (NCT00936702) Methods: Newly diagnosed, untreated CUP pts were eligible. Central pathology review confirmed CUP prior to registration; GEP was performed on formalin fixed tumor tissue. Pac (200 mg/m2), Carb (AUC=6) and E (30 mg once weekly) were delivered every 3 wks until progression or intolerable adverse events (AEs). The primary endpoint was confirmed response, with ≥11 of 50 responses (22%) needed for trial success. Secondary endpoints were OS, progression-free survival (PFS) and AEs. Results: 46 pts (median age 61) received a median 4 cycles (range: 1-33). 39 (85%), 21 (46%) and 1 (2%) experienced ≥1 grade (gr) 3+, 4+, or 5 (sepsis) AE, with gr 3+ hematologic AE most common (74%). Of 44 evaluable pts, 15 had a confirmed response (RR 34%, 95% CI: 21-50%), with a median PFS and OS of 4.1 and 10.1 mos, respectively. Adequate tissue for GEP was available in 36 pts and predicted 10 different sites of origin. In pts with a predicted tissue of origin in which taxane/platinum is standardly used, higher RR and significantly longer PFS and OS were observed compared with pts whose GEP identified a malignancy where taxane/platinum is not standard (Table). Conclusions: In pts with untreated CUP, Carb +Pac +E demonstrated promising antitumor activity. The GEP test identified patients clinically responsive to Carb/Pac/E therapy, and may be useful to select CUP pts for specific antitumor regimens. Clinical trial information: NCT00936702. [Table: see text]

scholarly journals Gene expression profiling and its use in adenocarcinomas of unknown primary origin: A case report

2015 ◽  
Vol 10 (4) ◽  
pp. 2657-2661
Author(s):  
ANA CEBOLLERO DE MIGUEL ◽  
ROBERTO PAZO CID ◽  
JAVIER MARTINEZ TRUFERO ◽  
ISABEL PAJARES BERNAD ◽  
LOURDES CALERA URQUIZU ◽  
...  
Keyword(s):  
Gene Expression ◽  
Case Report ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Unknown Primary ◽  
Primary Origin ◽  
Unknown Primary Origin

Gene-expression profiling and not immunophenotypic algorithms predicts prognosis in patients with diffuse large B-cell lymphoma treated with immunochemotherapy

Blood ◽  
2011 ◽  
Vol 117 (18) ◽  
pp. 4836-4843 ◽  
Author(s):  
Gonzalo Gutiérrez-García ◽  
Teresa Cardesa-Salzmann ◽  
Fina Climent ◽  
Eva González-Barca ◽  
Santiago Mercadal ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cell ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Tissue Microarrays ◽  
Prognostic Impact ◽  
Germinal Center B Cell ◽  
Large B Cell

Abstract Diffuse large B-cell lymphomas (DLBCLs) can be divided into germinal-center B cell–like (GCB) and activated-B cell–like (ABC) subtypes by gene-expression profiling (GEP), with the latter showing a poorer outcome. Although this classification can be mimicked by different immunostaining algorithms, their reliability is the object of controversy. We constructed tissue microarrays with samples of 157 DLBCL patients homogeneously treated with immunochemotherapy to apply the following algorithms: Colomo (MUM1/IRF4, CD10, and BCL6 antigens), Hans (CD10, BCL6, and MUM1/IRF4), Muris (CD10 and MUM1/IRF4 plus BCL2), Choi (GCET1, MUM1/IRF4, CD10, FOXP1, and BCL6), and Tally (CD10, GCET1, MUM1/IRF4, FOXP1, and LMO2). GEP information was available in 62 cases. The proportion of misclassified cases by immunohistochemistry compared with GEP was higher when defining the GCB subset: 41%, 48%, 30%, 60%, and 40% for Colomo, Hans, Muris, Choi, and Tally, respectively. Whereas the GEP groups showed significantly different 5-year progression-free survival (76% vs 31% for GCB and activated DLBCL) and overall survival (80% vs 45%), none of the immunostaining algorithms was able to retain the prognostic impact of the groups (GCB vs non-GCB). In conclusion, stratification based on immunostaining algorithms should be used with caution in guiding therapy, even in clinical trials.

Identifying the primary site using gene expression profiling in patients with carcinoma of an unknown primary (CUP): a feasibility study from the GEFCAPI

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22168-e22168
Author(s):  
Y. Loriot ◽  
M. Gross-Goupil ◽  
T. Lesimple ◽  
E. Blot ◽  
Y. Merrouche ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Phase Iii ◽  
Unknown Primary ◽  
Primary Cancer ◽  
Recommended Treatment ◽  
Dismal Prognosis ◽  
Diagnostic Biopsy

e22168 Background: CUP are an heterogeneous family of neoplasms with a dismal prognosis, with empiric chemotherapy as the recommended treatment. The aim of this study was to evaluate the feasibility of a 500-mRNA microarray to identify the tissue of origin in patients with CUP. Methods: Diagnostic biopsy formalin-fixed, paraffin-embedded (FFPE) specimens from 22 patients with CUP were prospectively collected. Gene expression profiling was performed using oligonucleotide microarray that contains 495 genes selected as highly differentially expressed between 49 tumor types (CupPrint). Results: The assay was successfully performed on specimens from 18 of the 22 patients (82%). It could not be performed because of a low RNA preservation in the remaining 4 cases. The median age was 57 years (range: 29–70 years). The median delay from tissue shipping to receipt of CupPrint result was 11 days (range: 1–26 days). The most common tissues of origin identified were lung cancer (22%) and colorectal cancer (17%). Of note, a primary cancer which would not be adequately treated by an empiric chemotherapy regimen currently recommended in CUP (like cisplatin-gemcitabine or carboplatin-paclitaxel) was identified in about half patients: kidney cancer (1), hepatocarcinoma (1), colorectal cancer (3), head and neck cancer (2) and cholangiocarcinoma (1). Conclusions: Gene expression profiling of FFPE biopsy specimens from patients with CUP is feasible in a reasonable delay, making it feasible in clinical practice. A phase III randomized trial is planned to compare therapy based on gene expression-suspected primary cancer versus empiric chemotherapy. No significant financial relationships to disclose.

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