Molecularly Guided Therapy Versus Continued Chemotherapy in Unfavorable Cancer of Unknown Primary: Updated Efficacy and Safety From the Randomized, Phase II CUPISCO Study
In brief
Molecularly guided therapy adds two months PFS in unfavorable CUP
In the phase II CUPISCO trial, patients with unfavorable cancer of unknown primary who received genome-based targeted treatment after initial chemotherapy experienced a median progression-free survival of 6.1 months versus 4.4 months with continued standard chemotherapy. Overall survival showed a modest, non-significant trend favoring the targeted approach, and safety was comparable, supporting early use of comprehensive genomic profiling.
- Journal
- Journal of clinical oncology : official journal of the American Society of Clinical Oncology (Q1)
- Published
- 3 September 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Alwin Krämer, Tilmann Bochtler, Chantal Pauli, Kai-Keen Shiu, Natalie Cook, Juliana Janoski de Menezes, et al.
- PMID
- 42691436
- DOI
- 10.1200/JCO-25-02974
Why clinicians should know about it
- Picked for Surgical Oncology (top studies of the week, 6 September 2026): High-quality evidence in a top journal
- Picked for Oncology and Radiation Oncology (top studies of the week, 6 September 2026): Phase II RCT, CGP-guided therapy improves PFS in CUP
- Picked for Radiation Oncology (top studies of the week, 6 September 2026): High-quality evidence in a top journal
Abstract
CUPISCO (ClinicalTrials.gov identifier: NCT03498521) demonstrated longer progression-free survival (PFS) with comprehensive genomic profiling (CGP) and subsequent molecularly guided therapies (MGTs), versus standard platinum-based chemotherapy, in patients with previously untreated, unfavorable cancer of unknown primary (CUP) who reached disease control after induction chemotherapy (three cycles). We report efficacy and safety after >1 year of additional follow-up. Eligible patients were randomly assigned (3:1) to MGT (investigator-chosen after discussion in a molecular tumor board) or three further cycles of chemotherapy. The primary end point was PFS. Secondary end points included overall survival (OS) and safety. At data cutoff (December 6, 2024), 436 patients were randomly assigned (326 to MGT; 110 to chemotherapy). Median follow-up was 37.0 months (range, 0.0-67.8). Updated median PFS was 6.1 months (95% CI, 4.7 to 6.5) with MGT and 4.4 months (95% CI, 4.2 to 6.4) with chemotherapy (hazard ratio [HR], 0.75 [95% CI, 0.59 to 0.95]; P = .017); median OS was 15.2 months (95% CI, 13.9 to 18.4) and 12.8 months (95% CI, 9.8 to 15.4), respectively (HR, 0.79 [95% CI, 0.61 to 1.02]; P = .0689). No new safety signals were identified. These updated results aligned with the primary analysis, demonstrating the benefit of CGP with subsequent MGT and highlighting the importance of incorporating CGP at initial diagnosis to guide treatment decisions for patients with unfavorable CUP.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.