Treatment of carcinoma of unknown primary site (CUP) directed by molecular profiling diagnosis: A prospective, phase II trial.

Abstract

10540 Background: Molecular profiling of biopsy specimens identifies a tissue of origin in the majority of CUP patients (pts). However, the value of these diagnoses in improving treatment efficacy is unknown. We present preliminary data from the first prospective evaluation of treatment based on molecular assay diagnoses in CUP pts. Methods: Surgical or core needle biopsies from previously untreated CUP pts were submitted for determination of a primary site by a 92-gene RT-PCR assay (CancerTYPE ID, bioTheranostics, Inc). Pts received standard first-line therapy for the cancer identified; pts unclassifiable by assay received empiric paclitaxel/carboplatin/bevacizumab/erlotinib. Study goals: 1) to evaluate the ability of the CancerTYPE ID assay to identify the tissue of origin in a prospective, unselected group of CUP pts, and 2) to obtain information regarding efficacy of assay-directed treatment. Results: Between 10/08 and 8/09, 110 pts were enrolled, and 66 received assay-directed therapy. 44 pts did not receive assay-directed treatment: became ineligible -15, insufficient tissue – 12, refused assay-directed treatment -8, required treatment prior to assay results – 7, assay results led to primary site detection - 2. Diagnoses were made in 61 of 66 pts (92%) and included: pancreas – 11, colorectal – 8, urinary bladder – 8, NSCLC – 5, ovary – 4, breast – 3, kidney – 3, gallbladder – 3, liver – 3, carcinoid – 3, skin (squamous) – 3, others – 7 (1 each). ORR and median PFS for the entire group were 32% and 7.4 months, respectively. The 8 colorectal cancer pts had typical distribution of metastases (liver, intra-abdominal) and had clinical benefit with FOLFOX/bevacizumab (3 PR, 5 SD). In other diagnostic groups, clinical features and response to treatment were generally as expected. Updated efficacy information on subgroups will be presented. Conclusions: Molecular profiling predicted a tissue of origin in most pts with CUP. Clinical features were generally consistent with the assay diagnosis, as were responses to directed therapy. These preliminary data are promising, and the study is ongoing to better evaluate the impact of molecular profiling on treatment outcomes. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Biotheranostics Biotheranostics, Genentech Biotheranostics Biotheranostics