Longer survival with precision medicine in late-stage cancer patients

C K Mapendano; A K Nøhr; M Sønderkær; A Pagh; A Carus; T Lörincz; C A Haslund; L Ø Poulsen; A Ernst; J S Bødker; S C Dahl; L Sunde; A H Brügmann; C Vesteghem; I S Pedersen; M Ladekarl

doi:10.1016/j.esmoop.2024.104089

Longer survival with precision medicine in late-stage cancer patients

ESMO Open. 2025 Jan 3;10(1):104089. doi: 10.1016/j.esmoop.2024.104089. Online ahead of print.

Authors

C K Mapendano¹, A K Nøhr², M Sønderkær³, A Pagh¹, A Carus⁴, T Lörincz¹, C A Haslund¹, L Ø Poulsen⁴, A Ernst³, J S Bødker³, S C Dahl², L Sunde⁵, A H Brügmann⁶, C Vesteghem⁷, I S Pedersen³, M Ladekarl⁸

Affiliations

¹ Department of Oncology and Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark.
² Center for Clinical Data Science, Aalborg University and Aalborg University Hospital, Aalborg, Denmark.
³ Molecular Diagnostics and Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
⁴ Department of Oncology and Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
⁵ Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Department of Clinical Genetics and Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark.
⁶ Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Department of Pathology, Aalborg University Hospital, Aalborg, Denmark.
⁷ Center for Clinical Data Science, Aalborg University and Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
⁸ Department of Oncology and Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark. Electronic address: morten.ladekarl@rn.dk.

PMID: 39754975
DOI: 10.1016/j.esmoop.2024.104089

Abstract

Background: In a per-protocol analysis of molecularly profiled patients with treatment-refractory, end-stage cancer discussed at the National Molecular Tumor Board (NMTB), we aimed to assess the overall survival (OS) outcome of targeted treatment compared with no targeted treatment.

Materials and methods: Patients were prospectively included at a single oncological center. Whole exome and RNA sequencing (tumor-normal) were carried out, and cases were presented at the NMTB for discussion of targeted treatment. Treatment was available through a basket trial, by compassionate use or in early clinical trials.

Results: One hundred and ninety-six patients were included from 2020 to 2023. In all but three patients a driver variant was disclosed, while 42% had simultaneous affection of more than three oncogenic pathways. In 42% of patients a druggable target was identified but two-thirds did not receive the suggested treatment. The fraction of patients initiating treatment yearly rose from 8% to 22%. For patients treated (N = 30), the clinical benefit rate was 44% and median time on treatment was 3.5 months. Druggable targets were enriched in lung cancers, while patients receiving or not receiving targeted treatment had similar clinical characteristics. The median OS was longer for patients receiving targeted treatment (15 months), but similar for patients with no druggable target and suggested targeted treatment not initiated (5 and 6 months, respectively) (P = 0.004). In multivariate analysis, targeted treatment (hazard ratio 0.43, confidence interval 0.25-0.72), few metastatic sites, and adenocarcinoma histology were predictive of improved OS while alterations of the RTK/RAS pathway were prognostically unfavorable.

Conclusions: Tissue-agnostic targeted treatment based on molecular tumor profiling is possible in an increasing fraction of end-stage cancer patients. In those who receive targeted treatment, results strongly suggest a significant survival benefit.

Keywords: clinical trial; molecular pathway analysis; precision medicine; prognosis; tissue agnostic.