Challenges relating to solid tumour brain metastases in clinical trials, part 1: patient population, response, and...

Area of Science:

• Neuro-oncology
• Clinical trial design
• Brain metastases research

Background:

• Therapeutic outcomes for brain metastases require improvement.
• Existing clinical trials for brain metastases face challenges hindering regulatory acceptance.
• Inconsistent methodology in patient selection, endpoint definition, and imaging schedules complicates trial interpretation.

Purpose of the Study:

• To critically review the current state of clinical trials for brain metastases.
• To identify key issues impacting the validity and acceptance of trial results.
• To propose consensus recommendations for improving future clinical trial design in neuro-oncology.

Main Methods:

• A critical review of existing clinical trials focusing on brain metastases.
• Analysis of common issues in patient heterogeneity, endpoint definitions, and treatment considerations.
• Examination of CNS imaging schedules and consequences of progressive disease detection.

Main Results:

• Key issues identified include heterogeneous patient enrollment and variable clinical endpoint definitions.
• Lack of consistent consideration for disease-specific, modality-specific, and treatment-specific factors.
• High variability in CNS imaging schedules and management of new or progressive brain metastases.

Conclusions:

• There is a need for standardized criteria in brain metastases clinical trials.
• The Response Assessment in Neuro-Oncology (RANO) working group aims to enhance trial design.
• Consensus recommendations are proposed to guide the development of future clinical trial criteria for brain tumors.