“Cancer of unknown primary” (CUP) refers to metastases occurring in the body without a detectable original tumor, making organ-specific chemotherapy or targeted drugs unavailable. A significant international study involving over 630 patients from 34 countries, published in The Lancet, explores potential treatments for CUP.
Led by Professor Dr. Alwin Krämer, the study analyzed cancer cells and genetic fragments in participants’ blood for known mutations that approved drugs can target. Approximately one-third of CUP patients had these mutations and treatment with the corresponding drugs notably extended progression-free survival and possibly overall survival.
Dr. Krämer, a senior physician at Heidelberg University Hospital and head of the “Carcinoma of Unknown Primary (CUP)” task force at the National Center for Tumor Diseases Heidelberg, leads the research.
The phase 2 trial “CUPISCO,” registered at ClinicalTrials.gov (NCT03498521), addresses the challenge of treating CUP, which comprises up to 5% of cancers with no detectable primary tumor, severely limiting treatment options.
Typically, these patients receive non-specific chemotherapy, resulting in an average survival time of less than one year. Previous studies indicated that therapies based on molecular analyses to determine the tissue of origin were no more effective than standard chemotherapy.
The CUPISCO study adopted a novel approach, focusing on the molecular characteristics and gene mutations of the tumor cells to identify effective targets for existing drugs.
The study included 636 patients with newly diagnosed unfavorable subtype CUP across 150 clinics. Initially, all patients underwent three cycles of standard chemotherapy.
Patients whose cancer was temporarily halted were divided into two groups: a control group of 110 patients receiving additional standard chemotherapy and 326 patients whose mutations were targeted with appropriate drugs. If no mutations were found, an immune checkpoint inhibitor was added to stimulate the body’s cancer defenses.
The study found that about a third of patients benefited from targeted therapy. On average, the time until cancer progression was four months longer for those receiving targeted therapy compared to standard therapy.
Some patients in the targeted therapy group did not experience further cancer progression by the study’s end, suggesting long-term disease control with a good response to the therapy.
The researchers believe that around one-third of patients could gain additional months to years of disease-free survival through targeted therapy, outperforming standard treatment.
The study continues with a follow-up period to determine definitive overall survival figures. The CUPISCO study is notable not only for its size but also for centralizing and publishing globally heterogeneous diagnostic criteria for CUP syndrome. This led to a new guideline for diagnosing and treating CUP.
The study also demonstrated that genetic analysis of tumor fragments from blood samples (liquid biopsy) is as reliable as tissue sample analysis, crucial for CUP patients who often lack sufficient biopsy material.
Results from the CUPISCO study have been integrated into European guidelines, recommending genetic analysis of the tumor genome for all newly diagnosed CUP patients to identify targeted treatment options.
This recommendation is included in the latest European guidelines for mutation analysis and precision medicine for advanced tumor diseases, published in the Annals of Oncology.
The findings underscore the importance of liquid biopsy in improving CUP patient care and the need for its approval alongside existing tissue-based tests for CUP diagnostics.
