key papersKey paper

CUPISCO: molecularly guided therapy versus chemotherapy after disease control in unfavourable cancer of unknown primary

In the first large randomised trial in cancer of unknown primary, choosing a targeted drug or immunotherapy from the tumour's genomic profile after three cycles of chemotherapy held the disease back for longer than simply continuing chemotherapy.

International open-label randomised phase 2 trial in which 636 patients with newly diagnosed unfavourable cancer of unknown primary received three cycles of platinum-based chemotherapy; the 436 with disease control were randomised 3:1 to molecularly guided therapy chosen by a tumour board from comprehensive genomic profiling or to three further cycles of the same chemotherapy.

Median progression-free survival was 6.1 months with molecularly guided therapy against 4.4 months with chemotherapy (hazard ratio 0.72). Overall survival data were immature.

Randomised controlled trialChanged practice436 participants49 citations

Authors

Krämer A, Bochtler T, Pauli C, et al.

Published

The Lancet, 2024

Full text

doi:10.1016/S0140-6736(24)00814-6 PubMed 39096924

Findings

Median progression-free survival 6.1 months with molecularly guided therapy versus 4.4 months with continued chemotherapy; hazard ratio 0.72.
About one third of enrolled patients progressed during induction and were never randomised.

What it means

Comprehensive genomic profiling at diagnosis is now justified for unfavourable cancer of unknown primary, with a switch to a matched drug after induction chemotherapy when an actionable target is found.

Caveats

Open-label, progression-free survival endpoint, and the benefit was modest in absolute terms.
Many patients had no actionable alteration and received drugs of uncertain value.