Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.
Nature Medicine (2023 )Cite this article Radius Arm
External comparator arms should be used when investigating novel therapies for gastrointestinal stromal tumor and other rare tumors to facilitate drug testing and regulatory approvals.
Rare cancers, although individually uncommon, account for approximately one-quarter of all malignancies. Population-based studies have consistently shown that patients with rare cancers have worse outcomes than those diagnosed with more common cancers1. Although several factors contribute to poor survival rates, this pattern is likely linked to the inherent difficulties of clinical drug development for rare tumors2. Conventional clinical trial designs typically demand large numbers of participants to reach conclusive results, which poses a methodological challenge in the case of rare cancers.
This is a preview of subscription content, access via your institution
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
Receive 12 print issues and online access
Rent or buy this article
Prices vary by article type
Prices may be subject to local taxes which are calculated during checkout
Gatta, G. et al.Lancet Oncol.18, 1022–1039 (2017).
Casali, PG et al.Ann.Oncol.26, 300–306 (2015).
Article CAS PubMed Google Scholar
Goodwin, P. J. et al. J. Clin. Oncol. 31, 1123–1124 (2013).
Schaefer, I. M. et al. Am. Soc. Clin. Oncol. Educ. Book. 42, 1–15 (2022).
PubMed PubMed Central Google Scholar
Demetrius, GD et al.Lancet 368, 1329–1338 (2006).
Article CAS PubMed Google Scholar
Demetrius, GD et al.Lancet 381, 295–302 (2013).
Article CAS PubMed Google Scholar
Blay, J. Y. et al.Lancet Oncol.21, 923–934 (2020).
Article CAS PubMed PubMed Central Google Scholar
Kang, YK et al.Lancet Oncol.14, 1175–1182 (2013).
Article CAS PubMed PubMed Central Google Scholar
Kurokawa, Y. et al.Ann.Oncol.33, 959–967 (2022).
Article CAS PubMed Google Scholar
Article CAS PubMed Google Scholar
Liu, N. et al.BMC Med. Res. Methodol.21, 111 (2021).
Article PubMed PubMed Central Google Scholar
Chvetzoff, G. et al.J. Natl Canc.Inst.95, 19–29 (2003).
Mishra-Kalyani, P. S. et al. Ann. Oncol. 33, 376–383 (2022).
Article CAS PubMed Google Scholar
Zer, A. et al.J. Clin.Oncol.34, 1469–1475 (2016).
Modi, ND et al.JAMA Oncol.8, 1310–1316 (2022).
Article PubMed PubMed Central Google Scholar
This work was funded in part by the FERO Foundation and the Asociación Española Contra el Cáncer (AECC CLSEN20004SERR), both through grants to C.S. The general work of M.C.H. has been supported by grants from the US Department of Veterans Affairs (1 I01 BX005358-01A1) and National Institutes of Health/National Cancer Institute (NIH/NCI; 1 R21 CA263400-01) and by philanthropic donations from the GIST Cancer Research Fund and the Jonathan David Foundation. The work of J.K.S. was supported by NIH/NCI R01 CA226803-01A1. We thank J. Carmona (scientific strategy office, VHIO) for critical review of this manuscript.
Department of Medical Oncology, Vall d’Hebron University Hospital, Barcelona, Spain
Sarcoma Translational Research Program, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
The Life Raft Group, Wayne, NJ, USA
Sara Rothschild & Denisse Evans
Oncology Data Science, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
Guillermo Villacampa & Víctor Navarro
The Institute of Cancer Research, London, UK
Portland VA Health Care System and Knight Cancer Institute, Oregon Health & Science University, Portland, OR, USA
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
Department of Medical Oncology, Center Léon Bérard, Lyon, France
Claude Bernard University, Lyon, France
Department of Surgery, Division of Surgical Oncology, University of California San Diego, La Jolla, CA, USA
Department of Pharmacology, University of California San Diego, San Diego, CA, USA
Case Comprehensive Cancer Center in Cleveland, Cleveland, OH, USA
Department of Medical Oncology, All India Institute of Medical Science (AIIMS), New Delhi, India
Division of Clinical Studies, The Royal Marsden NHS Foundation Trust, The Institute of Cancer Research, London, UK
Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA
You can also search for this author in PubMed Google Scholar
You can also search for this author in PubMed Google Scholar
You can also search for this author in PubMed Google Scholar
You can also search for this author in PubMed Google Scholar
You can also search for this author in PubMed Google Scholar
You can also search for this author in PubMed Google Scholar
You can also search for this author in PubMed Google Scholar
You can also search for this author in PubMed Google Scholar
You can also search for this author in PubMed Google Scholar
You can also search for this author in PubMed Google Scholar
You can also search for this author in PubMed Google Scholar
You can also search for this author in PubMed Google Scholar
You can also search for this author in PubMed Google Scholar
You can also search for this author in PubMed Google Scholar
You can also search for this author in PubMed Google Scholar
Correspondence to César Serrano.
C.S. has received research funding (institution) from IDRX, Blueprint, Karyopharm, Pfizer, Deciphera and Bayer; consulting fees (advisory role) from Newbay, Cogent, Immunicum AB, Deciphera and Blueprint; payment for lectures from Roche, PharmaMar, Deciphera, Bayer and Blueprint; and travel grants from Gilead, PharmaMar, Pfizer and Bayer AG. M.C.H. reports consulting roles for Blueprint, Deciphera, C Stone Pharmaceuticals, Zai Labs, Cogent and Theseus Pharmaceuticals, and patents, royalties and other intellectual property regarding a patent on treatment of GIST-licensed to Novartis. G.V. has received speaker’s fees from MSD, GSK, Pfizer and Pierre Fabre, and has held an advisory role with AstraZeneca. S.G. has received funding (institution) from IDRX, Theseus, Blueprint, Deciphera, BioAtla, Springworks, Merck, Eisai and Daiichi Sankyo; consulting fees from Immunicum, Deciphera, Blueprint and Kayothera; equity in Abbott Labs; and other fees from WCG (Ayala-DSMB). J.-Y.B. receives research support (institution) from Deciphera, Eisai, Roche, Pharmamar, Bayer, GSK and MSD. J.K.S. receives consultant fees from Deciphera, Aadi and Grand Rounds; serves as a consultant for CureMatch; has received speaker’s fees from Deciphera, Hoffman-La Roche, Foundation Medicine, Merck, QED and Daiichi Sankyo; and owns stock in Personalis. R.L.J. reports consulting or advisory roles for Lilly, Immune Design, Merck Serono, Adaptimmune, Daiichi Sankyo, Eisai, Morphotek, TRACON Pharma, Immodulon Therapeutics, Deciphera, PharmaMar, Blueprint Medicines Corporation, Clinigen Group, Epizyme, Boehringer Ingelheim, Bayer, Karma Oncology and UpToDate; research funding from GlaxoSmithKline; and reimbursement of travel and accommodation expenses from PharmaMar. P.R. has received honoraria for lectures and Advisory Board meetings from MSD, BMS, Novartis, Pierre Fabre, Sanofi, Merck, Philogen and Astra Zeneca outside of the scope of this study. N.S. has received consulting fees (advisory role) from Deciphera, Bayer, Boehringer-Ingelheim, Epizyme and Aadi Biosciences. J.C.T. consulted for Blueprint, Deciphera, Cogent, Daiichi-Sankyo, Foghorn, Bayer and Adcendo. Life Raft Group, where S.R. and D.E. are employed, has received program-related grants from Blueprint, Cogent Biosciences, Daichii Sankyo, Deciphera, Genentech, IDRx, Novartis, Pfizer and Theseus. The remaining authors declare no conflicts of interest.
Serrano, C., Rothschild, S., Villacampa, G. et al. Rethinking placebos: embracing synthetic control arms in clinical trials for rare tumors. Nat Med (2023). https://doi.org/10.1038/s41591-023-02578-z
DOI: https://doi.org/10.1038/s41591-023-02578-z
Anyone you share the following link with will be able to read this content:
Sorry, a shareable link is not currently available for this article.
Provided by the Springer Nature SharedIt content-sharing initiative
Nature Medicine (Nat Med) ISSN 1546-170X (online) ISSN 1078-8956 (print)
Coilover Suspension Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.