Trends in the characteristics, dose-limiting toxicities and efficacy of phase I oncology trials: The Cancer Research UK experience.

Wong, Hock Tsen; Barton, Claire; McLeod, Robert; Darby-Dowman, Rachel; McQuillan, Janette P.; Turner, Helen; Wan, Susan; Backholer, Zoe; Peters, Jane; Halford, Sarah

doi:10.1200/jco.2015.33.15_suppl.2534

Cited by 2 publications

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“…1,[4][5][6] To date, discussions of risk and benefit are largely informed by decades-old meta-analyses of phase I trials of conventional anticancer therapies: authors widely cite a low response rate of approximately 5%, together with a 0.5% risk of death from associated toxicities. [7][8][9][10][11][12] In the current era of precision medicine, the focus of anticancer therapy research has largely shifted from cytotoxic agents to more targeted drugs. With fewer anticipated off-target effects, as well as improved supportive care measures, the rates of risk and benefit may now be more favorable.…”

Section: Introductionmentioning

confidence: 99%

Revisiting Risk and Benefit in Early Oncology Trials in the Era of Precision Medicine: A Systematic Review and Meta-Analysis of Phase I Trials of Targeted Single-Agent Anticancer Therapies

Mackley

Fernandez

Fletcher

et al. 2021

JCO Precision Oncology

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PURPOSE Phase I trials are a crucial step in the evaluation of new cancer therapies. Historically, low rates of response (5%) and comparably high rates of death from toxicities (0.5%) have contributed to debates on the ethics and orientation of these trials. With the introduction of novel targeted therapies, a contemporary estimate is needed. METHODS We systematically searched PubMed, Embase, and ClinicalTrials.gov for reports of phase I oncology trials of single-agent targeted immunomodulators, molecularly targeted therapies, and antiangiogenic agents, published between January 2015 and July 2018. Adult and pediatric trials of solid and hematological malignancies were eligible. Treatment-related adverse events (grades 3, 4, and 5) and response rates (objective, complete, and partial) were extracted and analyzed. RESULTS One hundred and fifty-eight trial reports, covering 6,707 patients, were included. The rate of treatment-related deaths was 0.0% (95% CI, 0.0 to 0.1), while 13.2% of patients (9.5 to 17.3) experienced a grade 3 or 4 treatment-related toxicity. The combined objective response rate was 6.4% (4.6 to 8.5). Among trials using tumor biomarkers as eligibility criteria, the objective response rate was higher (12.0% [7.3 to 17.6] compared to 4.9% [2.5 to 5.7], P value < .01). The same was true of trials focusing on a single tumor type (13.4% [8.2 to 19.4]) compared to multiple tumor types (3.8% [2.5 to 5.3], P value < .01). CONCLUSION Reduced grade 5 risk and improved benefit appears to exist in modern phase I oncology trials, particularly in trials that target single tumor types and integrate biomarkers as eligibility criteria. These findings provide information to support informed consent discussions, highlight the need for improved reporting of phase I oncology trials, and provide direction for optimizing their design.

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Section: Introductionmentioning

confidence: 99%

Revisiting Risk and Benefit in Early Oncology Trials in the Era of Precision Medicine: A Systematic Review and Meta-Analysis of Phase I Trials of Targeted Single-Agent Anticancer Therapies

Mackley

Fernandez

Fletcher

et al. 2021

JCO Precision Oncology

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“…reductions in tumour size among 5%–10% patients) and 0.5% probability of fatal toxicities. 5–8 In areas such as neurodegenerative disease, recent meta-analyses suggest that the best place for patients to be in randomized trials of new drugs is in the placebo arm. 9 To say we can’t say anything more determinate about risk and benefit is to reject the canons of scientific evidence.…”

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confidence: 99%

Commentary on Kahrass et al: The sublime inertia of informed consent language in early phase clinical trials involving patients

Kimmelman

2020

Clinical Trials

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Trends in the characteristics, dose-limiting toxicities and efficacy of phase I oncology trials: The Cancer Research UK experience.

Cited by 2 publications

References 0 publications

Revisiting Risk and Benefit in Early Oncology Trials in the Era of Precision Medicine: A Systematic Review and Meta-Analysis of Phase I Trials of Targeted Single-Agent Anticancer Therapies

Revisiting Risk and Benefit in Early Oncology Trials in the Era of Precision Medicine: A Systematic Review and Meta-Analysis of Phase I Trials of Targeted Single-Agent Anticancer Therapies

Commentary on Kahrass et al: The sublime inertia of informed consent language in early phase clinical trials involving patients

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