DNA profiling of carcinoma of unknown primary should inform treatment

New research showed that 1 in 3 patients with carcinoma of unknown primary (CUP; when no primary tumour site of origin can be found) may not be adequately treated with standard chemotherapy but may be suitable for matched targeted treatment or immunotherapy based on DNA changes in their tumour [1,2].

Looking for DNA changes in 303 CUP tissue samples collected in 2018, Prof. Jeffrey Ross (Upstate Medical University, Syracuse, USA) and colleagues used cutting edge technology to reveal that 32% of the tumours investigated could have been targeted by the latest medicines [1]. The same technology is now being used in the ongoing prospective CUPISCO trial. This current study is being followed up by one in which patients with CUP are being randomised to individualised targeted treatment or immunotherapy based on genetic alternations in their tumour, or to standard platinum-based chemotherapy. Initial results are expected within the next few years.

The need for a greater understanding of CUP tumour biology and a wider range of targeted therapies is reinforced by results of the also reported GEFCAPI 04 trial [2]. Started in 2012, this study used gene expression technology to identify the most likely primary tumour source in patients with CUP. However, best available targeted and other treatment tailored to primary tumours failed to improve disease progression or survival compared with standard platinum–based chemotherapy.

“The GEFCAPI 04 results are disappointing but many of the patients had pancreatic, biliary, and other kinds of cancer which are extremely difficult to treat and for which there are no targeted treatments. In a small number of patients who had suspected primary cancers unlikely to respond to empiric chemotherapy, molecular testing allowed use of a targeted agent or better tailored chemotherapy or immunotherapy. But there were probably not enough to make a difference to the overall results of the study,” said presenting author Prof. Karim Fizazi (University of Paris Sud, France).

1. Ross J et al. ESMO Congress 2019. Abstract 1983PD_ PR.
2. Fizazi K et al. ESMO Congress 2019. Abstract LBA15_PR.

Posted on 26 November 201925 March 2024