Standard Site-Specific Therapy Based on Gene-Expression Profiling vs Empirical Chemotherapy for Cancer of Unknown Primary


Key Points

  • Standard site-specific therapy based on gene-expression profiling did not improve outcomes vs empirical therapy.
  • Outcomes were numerically better in patients with predicted tumor types categorized as more vs less responsive.

In a Japanese phase II trial reported in the Journal of Clinical Oncology, Hayashi et al found that standard site-specific treatment based on gene-expression profiling was not associated with better outcomes vs empirical paclitaxel and carboplatin in patients with cancer of unknown primary site.

Study Details

In the study, comprehensive gene-expression profiling was performed by microarray analysis, with an established algorithm used to predict tumor origin. A total of 101 evaluable previously untreated patients from 14 sites were randomly assigned to receive standard site-specific therapy (n = 50) or empirical paclitaxel and carboplatin (n = 51).

The primary endpoint was 1-year overall survival. Cancer types most commonly predicted were pancreatic cancer (21%), gastric cancer (21%), and lymphoma (20%).

Survival Outcomes

The data cutoff for efficacy analysis was in May 2017. Overall survival at 1 year was 44.0% in the site-specific treatment group vs 54.9% in the empirical paclitaxel and carboplatin group (P = .264). For site-specific treatment vs empirical paclitaxel and carboplatin, the median overall survival was 9.8 months vs 12.5 months (P = .896) and median progression-free survival was 5.1 months vs 4.8 months (P = .550).

For 30 patients in the 2 groups with predicted tumor types categorized as more responsive to treatment (eg, colorectal, breast, ovarian, kidney, prostate, bladder, non–small cell lung, and germ cell cancers, as well as lymphoma) vs 71 patients with less responsive predicted tumor types (eg, biliary tract, pancreatic, gastroesophageal, liver, cervix, endometrial, thyroid, and head and neck cancers, as well as mesothelioma), median overall survival was 16.7 vs 10.6 months (P = .116) and median progression-free survival was 5.5 vs 3.9 months (P = .018).

The investigators concluded, “Site-specific treatment that was based on microarray profiling did not result in a significant improvement in 1-year survival compared with empirical paclitaxel and carboplatin, although prediction of the original site seemed to be of prognostic value.”

Kazuhiko Nakagawa, MD, PhD, of the Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the West Japan Oncology Group and by grants from Health Labour Sciences Research of Japan and Japan Agency for Medical Research and Development. The study authors’ full disclosures can be found at

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