Abstract
Advances in the treatment of cancer have resulted in improved outcomes for patients, but improving the cure rate is a major unmet need. While testing new anticancer drugs in the earliest settings may be attractive as the chance of benefit may be greatest, it is also a setting where researchers must ensure patients are not harmed, by either over or undertreatment, or denial of timely standard curative treatments. The Methodology for the Development of Innovative Cancer Therapies Taskforce (MDICT) meets immediately before the ESMO-Targeted Anticancer Therapies (ESMO-TAT) meeting, usually held annually in Paris, France, to address questions that are considered important for early academic clinical trials. The focus of the MDICT 2024 was on early, signal-seeking phase clinical trials of new drugs conducted in the neoadjuvant (NEO) setting (NEO-ECTs) rather than pivotal confirmatory NEO trials (NEO-CONFs), which are typically phase III in design. Recommendations encompass four key concepts: patient engagement, reviewing risk-benefit ratio and clinical/ethical equipoise, the requirement for a randomization to reduce bias and allow robust conclusions to be drawn, and the selection of appropriate endpoints. The careful design of NEO-ECTs will allow the testing of new anticancer treatments in earlier disease settings where activity is hoped to result in higher cure rates, while also ensuring that patients are not harmed by delays to curative/definitive treatments nor by long-term or late-onset toxicity and morbidity. Additional research and investigation are required to further define and refine robust endpoints for use in this setting, including imaging, tissue and blood based endpoints.