Testing new anticancer drugs before curative locoregional therapies: MDICT 2024 recommendations

Area of Science:

• Oncology
• Clinical Trial Design
• Drug Development

Background:

• Improving cancer cure rates remains a critical unmet need despite advances in treatment.
• Early-phase clinical trials of novel anticancer drugs offer potential for greatest benefit but require careful patient safety considerations.
• The Methodology for the Development of Innovative Cancer Therapies Taskforce (MDICT) convenes to address challenges in early academic clinical trials.

Purpose of the Study:

• To focus on early, signal-seeking phase clinical trials of new drugs in the neoadjuvant (NEO) setting (NEO-ECTs).
• To provide recommendations for the design of NEO-ECTs to ensure patient safety and robust conclusions.
• To explore strategies for testing new anticancer treatments in earlier disease settings to potentially increase cure rates.

Main Methods:

• Recommendations developed by the MDICT taskforce, focusing on the 2024 meeting.
• Emphasis on four key concepts: patient engagement, risk-benefit ratio and clinical/ethical equipoise, randomization, and selection of appropriate endpoints.
• Distinguishing between early, signal-seeking NEO-ECTs and pivotal confirmatory NEO trials (NEO-CONFs).

Main Results:

• Recommendations encompass patient engagement, risk-benefit assessment, and clinical/ethical equipoise.
• Requirement for randomization is highlighted to reduce bias and enable robust conclusions.
• Selection of appropriate endpoints is crucial for evaluating treatment efficacy and safety.

Conclusions:

• Careful design of NEO-ECTs is essential for testing new anticancer treatments in early disease settings.
• The goal is to achieve higher cure rates while preventing patient harm from delayed or suboptimal treatment.
• Further research is needed to refine robust endpoints, including imaging, tissue, and blood-based markers.