Trial reportESMO open2025
The pathway alteration load is a pan-cancer determinant of outcome of targeted therapies: results from the Drug Rediscovery Protocol (DRUP).
Trial report in ESMO open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02925234 (A Dutch National Study on Behalf of the CPCT to Facilitate Patient Access to Commercially Available, Targeted Anti-cancer Drugs to Determine the Potential Efficacy in Treatment of Advanced Cancers With a Known Molecular Profile), which is not on this map. Cited by 3 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Dutch National Study on Behalf of the CPCT to Facilitate Patient Access to Commercially Available, Targeted Anti-cancer Drugs to Determine the Potential Efficacy in Treatment of Advanced Cancers With a Known Molecular Profile
Who cites it
3 citing papers in PubMed.
- Systematic identification of genomic nonresponse biomarkers to cancer therapies.ESMO real world data and digital oncology · 2026Article
- Molecular profiling and access to treatment for rare cancers in Europe.Nature communications · 2026Article
- Olaparib for patients with tumors harboring alterations in homologous recombination repair genes: Results from the drug rediscovery protocol.International journal of cancer · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMany patients with cancer exhibit primary or rapid secondary resistance to targeted therapy (TT). We hypothesized that a higher number of altered oncogenic signaling pathways [pathway alteration load (PAL)] would reduce the benefit of TT which only intervenes in one pathway. This hypothesis was tested in the Drug Rediscovery Protocol (DRUP). PATIENTS AND
methodsDRUP is a prospective, pan-cancer, non-randomized clinical trial (NCT02925234) that treats patients with therapy-refractory metastatic cancer and an actionable molecular profile using matched off-label targeted and immunotherapies. All patients treated with TT with available clinical outcomes and whole genome sequencing were included. PAL was determined based on driver gene alterations and correlated with clinical benefit rate (CBR), progression-free survival (PFS) and overall survival (OS). Outcomes were validated in the independent Hartwig Medical database of metastatic cancers.
resultsIn 154 patients treated with TT, the median PAL was 3. Patients with a PAL below median (n = 60) demonstrated a higher CBR (41.7% versus 25.5%, odds ratio 0.48, P = 0.051), longer PFS [median 4.7 versus 2.9 months, adjusted hazard ratio (aHR) 1.70, P = 0.020] and OS (median 13.7 versus 5.6 months, aHR 3.80, P < 0.001) compared with those with PAL ≥3. Two hundred and fifty-eight patients in the Hartwig database showed similar results for CBR (54.2% versus 36.7%, odds ratio 2.04, P = 0.009) and PFS (7.0 versus 4.2 months, aHR 1.55, P = 0.009).
conclusionsIn our population, PAL emerged as a pan-cancer determinant of outcome to TT. Our findings support refined patient selection for TT and highlight the rationale for combinatorial treatment strategies in patients with multiple affected pathways.
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