The Asco Post

Gene Profiling–guided Therapy May Improve Survival in Patients with Carcinoma of Unknown Primary

By Matthew Stenger
July 15, 2012, Volume 3, Issue 11

Molecular gene-expression profiling is an emerging technique to determine tissue of origin in patients with carcinoma of unknown primary, although the value of predictions from such profiling in improving treatment outcomes is unclear. In a prospective trial using tumor profiling results to direct site-specific therapy for patients with carcinoma of unknown primary, Frank A. Greco, MD, and colleagues at the Sarah Cannon Research Institute/Tennessee Oncology in Nashville have found that assay-directed therapy may improve survival.1

Half of Patients Had More Responsive Tumors

In this trial, a 92-gene real-time, reverse transcription polymerase chain reaction (RT-PCR) assay (CancerTYPE ID; bioTheranostics, Inc) was performed on tumor biopsies from previously untreated patients with carcinoma of unknown primary. Patients for whom a tissue of origin was predicted and who were treatment candidates were assigned standard site-specific first-line therapy. Between October 2008 and December 2011, 289 patients were enrolled and 252 had successful assays performed. Of these 252, 247 (98%) had a tissue of origin predicted, 224 were eligible for treatment, and 197 received assay-directed treatment.

Of the 224 eligible for treatment, 120 (54%) had assay diagnoses of tumor types known to derive substantial benefit from standard site-specific treatment, including 27 patients with bladder cancer, 26 with colorectal cancer, 24 with non–small cell lung cancer (NSCLC), 10 each with breast cancer and ovarian cancer, 9 with kidney cancer, 4 each with prostate cancer and germ cell cancer, and 6 with other types of cancer. The 104 patients with assay diagnoses of relatively resistant tumors included 45 with biliary tract cancer, 12 with pancreas cancer, 10 with gastroesophageal cancer, 7 with liver cancer, 5 each with sarcoma and cervical cancer, and 20 with other origins of malignancy.

Overall Survival with Assay-directed Therapy

The median overall survival for all treated patients was 10.8 months. Median overall survival for the 197 patents with assay-directed treatment was 12.2 months, vs 6.0 months for 27 patients receiving empiric therapy. Median overall survival in the 120 patients with assay diagnoses of more responsive tumor types was 12.8 months, significantly longer than the median overall survival of 7.4 months in those with relatively resistant types (P = .027). Among subgroups of more responsive tumor types, median overall survival was 30 months for ovarian cancer, 16 months for NSCLC, 12 months for colorectal and kidney cancer, and 9 months for pancreas cancer.

As stated by the investigators, “This is the first prospective trial in which molecular profiling has directed site-specific therapy in [patients with carcinoma of unknown primary]. Assay-directed therapy in 197 patients produced a median overall survival of 12.2 months that compares favorably with previous empiric carcinoma of unknown primary therapy…. Patients predicted to have more responsive tumor types had longer survival compared to less responsive types, suggesting accurate identification by the assay. These results strengthen the rationale for molecular profiling in [carcinoma of unknown primary] management.” ■

Disclosure: Dr. Greco has received honoraria from bioTheranostics.

Reference

1. Greco FA, Rubin MS, Boccia RV, et al: Molecular gene expression profiling to predict the tissue of origin and direct site-specific therapy in patients (pts) with carcinoma of unknown primary site (CUP): Results of a prospective Sarah Cannon Research Institute (SCRI) trial. 2012 ASCO Annual Meeting, Abstract 10530. Presented June 5, 2012.

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