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Clinical Studies

Efficacy-effectiveness analysis on survival in a population-based real-world study of BRAF-mutated metastatic colorectal cancer patients treated with encorafenib-cetuximab

British Journal of Cancer (2024)Cite this article

Subjects

Abstract

Background

Encorafenib-cetuximab has been approved for pretreated BRAFV600E-mutated metastatic colorectal cancer (mCRC) patients based on efficacy demonstrated in the randomized phase III BEACON trial. The aim of this real-world effectiveness study is to improve knowledge on the generalizability of trial results.

Methods

This population-based real-world study includes all mCRC patients in the Netherlands treated with encorafenib-cetuximab since approval. Individual patient data and pathology reports were collected. Overall survival (OS) was compared to BEACON and subgroup analyses were conducted for patients who would have been eligible and ineligible for BEACON.

Results

166 patients were included with a median follow-up time of 14.5 months. Median OS was 6.7 months (95% CI:6.0–8.3) and differed from BEACON (9.3 months; 95% CI:8.0–11.3, p-value 0.002). Thirty-six percent of real-world patients would have been ineligible for the BEACON trial. Trial ineligible subgroups with symptomatic brain metastases and WHO performance status ≥2 had the poorest median OS of 5.0 months (95% CI:4.0-NR) and 3.9 months (95% CI:2.4-NR).

Conclusion

This real-world cohort of mCRC patients treated with encorafenib-cetuximab showed a clinically relevant efficacy-effectiveness gap for OS. The chance of survival benefit from encorafenib-cetuximab in patients with brain metastases and/or WHO performance status ≥2 is negligible as neither efficacy nor effectiveness has been demonstrated.

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Fig. 1: Kaplan–Meier estimates of the overall survival of mCRC patients treated with encorafenib-cetuximab.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors thank the registration team of the Netherlands Comprehensive Cancer Organization (IKNL) for the collection of data for the Netherlands Cancer Registry as well as IKNL staff for scientific advice. The authors also thank the registration team of the nationwide network and registry of histo- and cytopathology in the Netherlands (PALGA) for collection of mutation status in the Dutch cohort.

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Authors and Affiliations

  1. Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands

    Koen Zwart, Sietske C. M. W. van Nassau, Frederieke H. van der Baan, Miriam Koopman, Geraldine R. Vink & Jeanine M. L. Roodhart

  2. Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands

    Frederieke H. van der Baan

  3. Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands

    Petur Snaebjornsson

  4. Department of Research and Development, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, The Netherlands

    Anna J. van Gestel & Geraldine R. Vink

Authors
  1. Koen Zwart
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Contributions

KZ: Conceptualization, Methodology, Software, Validation, Formal analysis, Investigation, Data curation, Writing – original draft, Writing – review & editing, Visualization. SN: Conceptualization, Investigation, Data curation, Writing – original draft, Writing – review & editing. FB: Methodology, Writing – review & editing, Supervision. MK: Conceptualization, Writing – review & editing, Supervision. PS: Writing – review & editing, Supervision. AG: Software, Writing – review & editing. GV: Conceptualization, Writing – review & editing, Project administration. JR: Conceptualization, Writing – review & editing, Supervision.

Corresponding author

Correspondence to Jeanine M. L. Roodhart.

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Competing interests

KZ: Received research funding via institution from Bristol-Myers Squibb. SN: Received research funding via institution from Pierre-Fabre. Had travel, accommodations, or other expenses paid or reimbursed via institution by Servier. FB: Received research funding via institution from Bristol-Myers Squibb. MK: Received research funding via institution from Bayer, Bristol-Myers Squibb, Merck-Serono, Pierre Fabre, Servier, Roche, Sanofi, and Personal Genome Diagnostics. PS: Consulting or advisory role for Bayer, Bristol-Myers Squibb, MEDtalks via institution. AG: No competing interests. GV: Consulting or advisory role for Merck via institution. Received research funding via institution from Merck, Bayer, Personal Genome Diagnostics, Delphi Diagnostics, Bristol-Myers Squibb, Sirtex Medical. JR: Consulting or advisory role for Bayer, Bristol-Myers Squibb, Merck-Serono, Pierre Fabre, Servier via institution. Received research funding via institution from Bayer, Bristol-Myers Squibb, Merck-Serono, Pierre Fabre, Servier, HUB 4 organoids, and Cleara Biotech. Had travel, accommodations, or other expenses paid or reimbursed via institution by Servier.

Ethics approval and consent to participate

According to the Central Committee on Research involving Human Subjects, this type of registry-based study does not require approval from an ethics committee in the Netherlands. The study was approved by the Privacy Review Board and the scientific council of the Netherlands Comprehensive Cancer Organization (IKNL) which collects and guards the data for the Netherlands Cancer Registry (NCR). All data were pseudonymized prior to the transfer from IKNL to the researchers. The NCR uses an opt-out approach to consent. The study was performed in accordance with the Declaration of Helsinki.

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Zwart, K., van Nassau, S.C.M.W., van der Baan, F.H. et al. Efficacy-effectiveness analysis on survival in a population-based real-world study of BRAF-mutated metastatic colorectal cancer patients treated with encorafenib-cetuximab. Br J Cancer (2024). https://doi.org/10.1038/s41416-024-02711-w

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