The approval of therapeutic agents that are tested in patients deemed ineligible for intensive or aggressive therapy is increasingly popular. This approach enables comparisons of novel therapies with less-aggressive agents, as well as data from nonrandomized studies to be used for market authorization. Herein, we discuss three mechanisms that could be adopted to avoid the temptation of applying this strategy excessively.
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Cortes, J. E. et al. Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Leukemia 33, 379–389 (2018).
Mateos, M.-V. et al. Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma. N. Engl. J. Med. 378, 518–528 (2018).
DiNardo, C. D. et al. Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study. Lancet Oncol. 19, 216–228 (2018).
Balar, A. V. et al. First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study. Lancet Oncol. 18, 1483–1492 (2017).
U.S. Food and Drug Administration. 2009 meeting materials, Oncologic Drugs Advisory Committee. FDA https://wayback.archive-it.org/7993/20170403224034/https://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/ucm126185.htm (updated 24 Feb 2015).
Woyach, J. A. et al. Ibrutinib regimens versus chemoimmunotherapy in older patients with untreated CLL. N. Engl. J. Med. 379, 2517–2528 (2018).
Tao, D. & Prasad, V. Choice of control group in randomised trials of cancer medicine: are we testing trivialities? Lancet Oncol. 19, 1150–1152 (2018).
Durie, B. G. M. et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet 389, 519–527 (2017).
The work of V.P. is funded by the Laura and John Arnold Foundation.
R.J.C. reports receiving consulting fees from Syros. V.P. receives royalties from his book Ending Medical Reversal, has received honoraria for Grand Rounds or lectures from several universities, medical centres, non-profit groups and professional societies and is a writer for Medscape. J.G. declares no competing interests.