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

Source: https://onco.cc/key-papers/paper-cupisco-molecularly-guided-therapy-cup-lancet-2024/  
OnCo record `paper-cupisco-molecularly-guided-therapy-cup-lancet-2024` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Summary

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-18
- Journal: The Lancet
- Year: 2024
- DOI: 10.1016/S0140-6736(24)00814-6
- Authors: Krämer A, Bochtler T, Pauli C, et al.
- 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.

## Sources

- Lancet 2024: https://doi.org/10.1016/S0140-6736(24)00814-6
- PubMed: https://pubmed.ncbi.nlm.nih.gov/39096924/

## Connected records

- cancers: [Cancer of unknown primary, unfavourable (adenocarcinoma and poorly differentiated carcinoma)](https://onco.cc/cancers/cup-unfavourable/)
- drugs: [Carboplatin](https://onco.cc/drugs/carboplatin/), [Gemcitabine + cisplatin](https://onco.cc/drugs/gemcitabine-cisplatin/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/)
- trials: [CUPISCO](https://onco.cc/trials/cupisco/)
- journals: [The Lancet](https://onco.cc/journals/lancet/)

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