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Critical evaluation of the ProfiLER-02 study design and outcomes

Nature Medicine volume 31, pages 3290–3291 (2025)Cite this article

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Matters Arising to this article was published on 10 September 2025

The Original Article was published on 07 April 2025

arising from Olivier Trédan et al. Nature Medicine https://doi.org/10.1038/s41591-025-03613-x (2025)

The ProfiLER-02 study, discussed in ref. 1, represents a significant randomized controlled trial examining genomic testing approaches in cancer treatment. The study compared comprehensive genetic testing (324 genes) versus limited testing (87 genes) in 339 patients with advanced solid tumors to determine which approach yielded better treatment recommendations and clinical outcomes1. The comprehensive genetic panel demonstrated superior identification of potential treatments, detecting actionable targets in 52% of patients compared to 37% with the smaller panel, a notable 15%-point increase. Additionally, more patients received molecularly-targeted treatments with comprehensive testing (14% versus 9%). However, despite identifying more treatment options, the study found no improvement in patient survival or treatment response rates, highlighting a critical gap between genomic discovery and clinical benefit1. While this randomized controlled trial represents a valuable effort to provide patients with access to testing, several methodological limitations in its design, implementation and analysis may limit its generalizability and leave important questions for future research to address.

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References

  1. Trédan, O. et al. Broad versus limited gene panels to guide treatment in patients with advanced solid tumors: a randomized controlled trial. Nat. Med. 31, 1502–1508 (2025).

    Article  PubMed  PubMed Central  Google Scholar 

  2. Sicklick, J. K. et al. Molecular profiling of cancer patients enables personalized combination therapy: the I-PREDICT study. Nat. Med. 25, 744–750 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Le Tourneau, C. et al. Molecularly targeted therapy based on tumour molecular profiling versus conventional therapy for advanced cancer (SHIVA): a multicentre, open-label, proof-of-concept, randomised, controlled phase 2 trial. Lancet Oncol. 16, 1324–1334 (2015).

    Article  PubMed  Google Scholar 

  4. Le Tourneau, C. & Kurzrock, R. What have we learned from SHIVA? Nat. Rev. Clin. Oncol. 13, 719–720 (2016).

    Article  PubMed  Google Scholar 

  5. Massard, C. et al. High-throughput genomics and clinical outcome in hard-to-treat advanced cancers: results of the MOSCATO 01 trial. Cancer Discov. 7, 586–595 (2017).

    Article  CAS  PubMed  Google Scholar 

  6. Hendriks, L. E. L. et al. Non-small-cell lung cancer. Nat. Rev. Dis. Prim. 10, 71 (2024).

    Article  PubMed  Google Scholar 

  7. Cercek, A. et al. PD-1 blockade in mismatch repair–deficient, locally advanced rectal cancer. N. Engl. J. Med. 386, 2363–2376 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Subbiah, V. & Kurzrock, R. Universal germline and tumor genomic testing needed to win the war against cancer: genomics is the diagnosis. J. Clin. Oncol. 41, 3100–3103 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Fletcher, L. The $100 genome: where’s the limit? https://frontlinegenomics.com/the-100-genome-wheres-the-limit/ (2025).

  10. Subbiah, V. Tissue-agnostic cancer therapies: promise, reality, and the path forward. Nat. Commun. 16, 4972 (2025).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

R.K. is funded in part by 5U01CA180888-08 and 5UG1CA233198-05.

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Authors and Affiliations

  1. Sarah Cannon Research Institute, Nashville, TN, USA

    Vivek Subbiah

  2. Genomic Sciences and Precision Medicine Center and Medical College of Wisconsin Cancer Center, Milwaukee, WI, USA

    Razelle Kurzrock

  3. WIN Consortium, Paris, France

    Razelle Kurzrock

  4. University of Nebraska–Lincoln, Lincoln, NE, USA

    Razelle Kurzrock

Authors
  1. Vivek Subbiah
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  2. Razelle Kurzrock
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Contributions

V.S. and R.K. reviewed the relevant literature, wrote the initial draft and critically revised the manuscript for final submission. V.S. and R.K. approved the final version.

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Correspondence to Vivek Subbiah.

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Competing interests

V.S. reports research funding for clinical trials paid to the institution from AbbVie, Agensys, Alfasigma, Altum, Amgen, Bayer, BERG Health, Blueprint Medicine, Boston Biomedical, Boston Pharmaceuticals, D3 Bio, Dragonfly Therapeutics, Exelixis, Fujifilm, GlaxoSmithKline, Idera Pharmaceuticals, Incyte, Inhibrix, Eli Lilly/Loxo Oncology, MedImmune, NanoCarrier, Novartis, PharmaMar, Pfizer, Relay Therapeutics, Roche/Genentech, Takeda and Turning Point Therapeutics; consulting/advisory role (paid to institution) from AbbVie, Astex Pharmaceuticals, AstraZeneca, Bayer, Genmab, Incyte, Lilly/Loxo Oncology, Novartis, Obsidian Therapeutics, Pfizer, Pheon Therapeutics, Regeneron, Relay Therapeutics, Roche, Endeavor Biomedicines, RevMed and LabGenius therapeutics; and other consulting/advisory role/CME from Helsinn Healthcare, Jazz Pharmaceuticals, Incyte, Loxo Oncology/Lilly, Novartis, Relay Therapeutics, Daiichi Sankyo, Illumina, Bayer, Medscape, OncLive, Clinical Care Communications, PERS and Med learning group. R.K. has received research funding from Biological Dynamics, Boehringer, Caris, Datar Genomics, Ingelheim, Debiopharm, Foundation Medicine, Genentech, Grifols, Guardant, Incyte, Konica Minolta, Medimmune, Merck Serono, Omniseq, Pfizer, Sequenom, Takeda and TopAlliance; as well as consultant and/or speaker fees and/or advisory board for Actuate Therapeutics, AstraZeneca, Bicara Therapeutics, Biological Dynamics, Caris, Daiichi Sankyo, EISAI, EOM Pharmaceuticals, Iylon, Merck, NeoGenomics, Neomed, Pfizer, Prosperdtx, F. Hoffmann-La Roche AG, TD2/Volastra, Turning Point Therapeutics and X-Biotech; has an equity interest in CureMatch, CureMetrix and IDbyDNA; serves on the Board of CureMatch and CureMetrix; and is a co-founder of CureMatch. The content is solely the responsibility of the authors and does not necessarily represent the official views of the institutions.

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Subbiah, V., Kurzrock, R. Critical evaluation of the ProfiLER-02 study design and outcomes. Nat Med 31, 3290–3291 (2025). https://doi.org/10.1038/s41591-025-03959-2

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