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Neurooncol Adv
Neurooncol Adv
noa
Neuro-Oncology Advances
2632-2498
Oxford University Press US

10.1093/noajnl/vdae090.114
vdae090.114
Final Category: Research Methods and Trial Design Considerations
AcademicSubjects/MED00300
AcademicSubjects/MED00310
RMTD-07 LOST CHANCES: THE SYSTEMATIC EXCLUSION OF PATIENTS WITH BRAIN METASTASIS IN EARLY-PHASE ONCOLOGY TRIALS
Fernandes Italo Sunnybrook Health Sciences Centre, Toronto/ON, Canada

Carmona-Gonzalez Carlos A Sunnybrook Health Sciences Centre, Toronto/ON, Canada

Suthaaharan Shonekaa McMaster University, Hamilton/ON, Canada

Sandhu Serena Serena McMaster University, Hamilton/ON, Canada

Menjak Ines Sunnybrook Health Sciences Centre, Toronto/ON, Canada

Smoragiewicz Martin Sunnybrook Health Sciences Centre, Toronto/ON, Canada

Jerzak Katarzyna Sunnybrook Health Sciences Centre, Toronto/ON, Canada

8 2024
02 8 2024
02 8 2024
6 Suppl 1 2024 SNO/ASCO CNS Metastases Conference i34i35
© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

Abstract

RATIONALE

Historically, cancer trials have often excluded patients with brain metastases (BrM). This limits our understanding of CNS-specific drug efficacy. We aimed to determine the proportion of phase I clinical trials for patients with solid tumors that exclude patients with BrM.

METHODS

In March 2023, a systematic search of the clinicaltrials.gov website was performed. Results are described as frequencies and compared using the Pearson’s chi-square or Cochran-Armitage tests.

RESULTS

1,714 phase I trials were identified and 990 met inclusion criteria. Most trials spanned several tumor types (n=659, 66.6%) and were registered between 2000- 2023 (n=884, 89.3%). Trials were mainly conducted in Asia (n=95, 9.6%), Europe (n=112, 11.3%), and North America (n=619, 62.5%). Categories of investigational agents were: targeted therapy (n=496, 50.1%), cytotoxic chemotherapy (n=118, 11.9%), immunotherapy (n=73, 7.37%); the most common combinations included chemotherapy plus targeted therapy (n=265, 26.8%) and chemotherapy plus immunotherapy (n=14, 1.4%). Patients with BrM were included in 25.1% (n=248) trials, included under certain conditions in 53.6% (n= 521), and excluded in the remaining 22.3% (n=221) of trials. Recent trials (2015-2019) were less likely to exclude patients with BrM compared to trials conducted between 2000-2004 (18% vs 38%, p=0.003). Exclusion of patients with BrM was less common in trials focusing on melanoma (16%), breast (15%) and lung (14%) cancer. Trials involving the use of cytotoxic chemotherapy were significantly more likely to exclude patients with BrM (n=58, 49%) than those employing targeted therapy (n= 110, 22%) or immunotherapy (n=15, 21%) (p=0.016). Trial location and stage of disease were not associated with exclusion of patients with BrM.

CONCLUSION

Recent phase I trials, particularly those evaluating the use of targeted therapy and/or immunotherapy, have a low rate of exclusion of patients with BrM compared to previous cytotoxic trials. However, many opportunities to test drugs with potential CNS efficacy are still lost.
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