The French multicentric molecular analysis platforms and personalized medicine trials MOST, MOST Plus and MEGAMOST
DOI:
https://doi.org/10.2340/1651-226X.2024.32745Keywords:
Personalized oncology, molecular analysis, oncology, sorafenib, olaparibAbstract
Background and purpose: In this manuscript we describe the academic French multicentric molecular analysis platforms including PROFILER, promoted by Centre Léon Berard, and the multicentric personalized medicine trials MOST, MOST Plus and MEGAMOST.
Patients/material and methods: MOST, MOST Plus and MEGAMOST comprise 14 cohorts with different targeted agents and immunotherapies.
Results and interpretation: PROFILER has recruited 5,991 patients in 10 years, MOST and MOST Plus 875 patients since 2014 and MEGAMOST 172 patients since 2020, and are still ongoing. We provide a description of the local, national and international implications of these initiatives, and we review the results of the sorafenib and olaparib cohorts.
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References
Massard C, Michiels S, Ferté C, et al. High-throughput genomics and clinical outcome in hard-to-treat advanced cancers: results of the MOSCATO 01 trial. Cancer Discov. 2017;7(6):586–95.
https://doi.org/10.1158/2159-8290.CD-16-1396 DOI: https://doi.org/10.1158/2159-8290.CD-16-1396
Trédan O, Wang Q, Pissaloux D, et al. Molecular screening program to select molecular-based recommended therapies for metastatic cancer patients: analysis from the ProfiLER trial. Ann Oncol Off J Eur Soc Med Oncol. 2019 May;30(5):757–65.
https://doi.org/10.1093/annonc/mdz080 DOI: https://doi.org/10.1093/annonc/mdz080
Le Tourneau C, Delord J-P, Gonçalves A, 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. 2015 Oct;16(13):1324–34.
https://doi.org/10.1016/S1470-2045(15)00188-6 DOI: https://doi.org/10.1016/S1470-2045(15)00188-6
Debien V, Vignot S, Massard C, et al. Molecular analysis for refractory rare cancers: sequencing battle continues – learnings for the MOSCATO-01 study. Crit Rev Oncol Hematol. 2023 Jan;181:103888.
https://doi.org/10.1016/j.critrevonc.2022.103888 DOI: https://doi.org/10.1016/j.critrevonc.2022.103888
Hoes LR, van Berge Henegouwen JM, van der Wijngaart H, et al. Patients with rare cancers in the drug rediscovery protocol (DRUP) benefit from genomics-guided treatment. Clin Cancer Res. 2022 Apr;28(7):1402–11.
https://doi.org/10.1158/1078-0432.CCR-21-3752 DOI: https://doi.org/10.1158/1078-0432.CCR-21-3752
PCM4EU – YouTube [Internet]. [cited 29-11-2023]. Available from: https://www.youtube.com/@PCM4EU/videos
Cassier PA, Peyramaure C, Attignon V, et al. Precision medicine for patients with gastro-oesophageal cancer: a subset analysis of the ProfiLER program. Transl Oncol. 2022 Jan;15(1):101266.
https://doi.org/10.1016/j.tranon.2021.101266 DOI: https://doi.org/10.1016/j.tranon.2021.101266
Bonnet E, Haddad V, Quesada S, et al. Alterations in homologous recombination-related genes and distinct platinum response in metastatic triple-negative breast cancers: a subgroup analysis of the ProfiLER-01 trial. J Pers Med. 2022 Sep;12(10):1595.
https://doi.org/10.3390/jpm12101595 DOI: https://doi.org/10.3390/jpm12101595
Bonneville-Levard A, Frappaz D, Tredan O, et al. Molecular profile to guide personalized medicine in adult patients with primary brain tumors: results from the ProfiLER trial. Med Oncol. 2021 Nov;39(1):4.
https://doi.org/10.1007/s12032-021-01536-4 DOI: https://doi.org/10.1007/s12032-021-01536-4
Varnier R, Le Saux O, Chabaud S, et al. Actionable molecular alterations in advanced gynaecologic malignancies: updated results from the ProfiLER programme. Eur J Cancer. 2019 Sep;118:156–65.
https://doi.org/10.1016/j.ejca.2019.06.017 DOI: https://doi.org/10.1016/j.ejca.2019.06.017
Arnaud-Coffin P, Brahmi M, Vanacker H, et al. Therapeutic relevance of molecular screening program in patients with metastatic sarcoma: analysis from the ProfiLER 01 trial. Transl Oncol. 2020 Dec;13(12):100870.
https://doi.org/10.1016/j.tranon.2020.100870 DOI: https://doi.org/10.1016/j.tranon.2020.100870
Benezech S, Saintigny P, Attignon V, et al. Tumor molecular profiling: pediatric results of the ProfiLER study. JCO Precis Oncol. 2020 Dec;(4):785–95.
https://doi.org/10.1200/PO.20.00023 DOI: https://doi.org/10.1200/PO.20.00023
Plan France Médecine Génomique 2025 [Internet]. PFMG; 2025 [cited 29-11-2023]. Available from: https://pfmg2025.aviesan.fr/
Berry DA. Bayesian clinical trials. Nat Rev Drug Discov. 2006 Jan;5(1):27–36.
https://doi.org/10.1038/nrd1927 DOI: https://doi.org/10.1038/nrd1927
Trédan O, Toulmonde M, Le Tourneau C, et al. Sorafenib in molecularly selected cancer patients: final analysis of the MOST-plus Sorafenib cohort. Cancers. 2023 Jun;15(13):3441.
https://doi.org/10.3390/cancers15133441 DOI: https://doi.org/10.3390/cancers15133441
Gelderblom H, Cropet C, Chevreau C, et al. Nilotinib in locally advanced pigmented villonodular synovitis: a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2018 May;19(5):639–48.
https://doi.org/10.1016/S1470-2045(18)30143-8 DOI: https://doi.org/10.1016/S1470-2045(18)30143-8
Polito M, Tourneau CL, DeMontfort A, et al. 138P Precision medicine phase II study evaluating the efficacy of olaparib in patients with progressive solid cancers and carriers of homologous recombination repair genes alterations. Ann Oncol. 2023 Oct;34:S236.
https://doi.org/10.1016/j.annonc.2023.09.2863 DOI: https://doi.org/10.1016/j.annonc.2023.09.2863
Clinical development success rates and contributing factors 2011–2020 [Internet]. BIO [cited 29-11-2023]. Available from: https://www.bio.org/clinical-development-success-rates-and-contributing-factors-2011-2020
Thomas DW, Burns J, Audette J, et al. Clinical development success rates 2006–2015. San Diego, CA: Biomedtracker; 2016.
van der Velden DL, Hoes LR, van der Wijngaart H, et al. The drug rediscovery protocol facilitates the expanded use of existing anticancer drugs. Nature. 2019 Oct;574(7776):127–31.
https://doi.org/10.1038/s41586-019-1600-x DOI: https://doi.org/10.1038/s41586-019-1600-x
Geurts B, Zeverijn LJ, Battaglia TW, et al. Efficacy and predictors of response of nivolumab in treatment-refractory MSI solid tumors: results of a tumor-agnostic DRUP cohort. J Clin Oncol. 2023 Jun;41(16_suppl):2590.
https://doi.org/10.1200/JCO.2023.41.16_suppl.2590 DOI: https://doi.org/10.1200/JCO.2023.41.16_suppl.2590
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Copyright (c) 2023 Loic Verlingue, Marine Desevre, Marie Polito, Gwenaelle Garin, Christine Rodriguez, Wang Qing, Olivier Tredan, David Perol, Isabelle Ray-Coquard, Sylvie Chabaud, Jean Yves Blay
This work is licensed under a Creative Commons Attribution 4.0 International License.
