Precision oncology has reached a milestone as data from two trials in which molecular profiling guided both site-specific and tumour-agnostic therapies indicate improved survival outcomes in patients with cancer of unknown primary. These findings can also be extrapolated and support the use of tissue-agnostic approaches in general, and also suggest that the tissue of origin might have a role in the agnostic classification of cancers and their response to treatment.
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References
André, F., Rassy, E., Marabelle, A., Michiels, S. & Besse, B. Forget lung, breast or prostate cancer: why tumour naming needs to change. Nature 626, 26–29 (2024).
Liu, X. et al. Site-specific therapy guided by a 90-gene expression assay versus empirical chemotherapy in patients with cancer of unknown primary (Fudan CUP-001): a randomised controlled trial. Lancet Oncol 25, 1092–1102 (2024).
Krämer, A. et al. Molecularly guided therapy versus chemotherapy after disease control in unfavourable cancer of unknown primary (CUPISCO): an open-label, randomised, phase 2 study. Lancet 404, 527–539 (2024).
Pavlidis, N. & Pentheroudakis, G. Cancer of unknown primary site. Lancet 379, 1428–1435 (2012).
Hayashi, H. et al. Randomized phase II trial comparing site-specific treatment based on gene expression profiling with carboplatin and paclitaxel for patients with cancer of unknown primary site. J. Clin. Oncol 37, 570–579 (2019).
Fizazi, K. et al. LBA15_PR - a phase III trial of empiric chemotherapy with cisplatin and gemcitabine or systemic treatment tailored by molecular gene expression analysis in patients with carcinomas of an unknown primary (CUP) site (GEFCAPI 04). Ann. Oncol. 30, v851 (2019).
Rassy, E. & Pavlidis, N. Progress in refining the clinical management of cancer of unknown primary in the molecular era. Nat. Rev. Clin. Oncol. 17, 541–554 (2020).
Rassy, E. et al. Systematic review of the CUP trials characteristics and perspectives for next-generation studies. Cancer Treat. Rev. 107, 102407 (2022).
Hernando-Calvo, A., Rossi, A., Vieito, M., Voest, E. & Garralda, E. Agnostic drug development revisited. Cancer Treat. Rev. 128, 102747 (2024).
Westphalen, C. B. et al. The ESMO Tumour-Agnostic Classifier and Screener (ETAC-S): a tool for assessing tumour-agnostic potential of molecularly guided therapies and for steering drug development. Ann. Oncol. https://doi.org/10.1016/j.annonc.2024.07.730 (2024).
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E.R. has received honoraria from Eli Lilly, Novartis and Seagen; has received travel support from Gilead, Mundipharma, Novartis, Pfizer and Roche; and research funding from Gilead, Menarini and MSD. F.A. has acted as a consultant and/or adviser of AstraZeneca, Daiichi–Sankyo, Lilly, Novartis, Pfizer, Relay Tx and Roche; has received travel support from Astrazeneca, GlaxoSmithKline, Lilly, Novartis and Roche; and has received research funding from AstraZeneca, Daiichi, Eli Lilly, Novartis, Pfizer and Roche.
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Rassy, E., André, F. New clinical trials in CUP and a novel paradigm in cancer classification. Nat Rev Clin Oncol (2024). https://doi.org/10.1038/s41571-024-00942-7
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DOI: https://doi.org/10.1038/s41571-024-00942-7
