ESMO 2025 – Proffered paper session
Villejuif, 18 October 2025
Can cancer be prevented with medication? A look back at 40 years of clinical trials.
Dr Alexandre Xu-Vuillard presents at the ESMO congress the results of DRUGPREV, the first large-scale retrospective study dedicated to pharmacological prevention of cancer. The researchers critically analysed around one hundred trials conducted since 1980, to evaluate the effectiveness of different molecules (vitamins, anti-inflammatories, etc.) in preventing the onset of the disease. This work made it possible to identify effective approaches, learn from failures, and propose recommendations to guide the development of future preventive treatments. DRUGPREV provides a unique overview of forty years of research in this still largely underexplored field, while the number of new cancer cases reported each year worldwide continues to rise.
Abstract No. 2274O presented orally by Dr Alexandre Xu-Vuillard on Saturday 18 October at 15:30.
This oral presentation is among the 60 studies on the programme for the 2025 edition of ESMO presented by a physician-researcher from Gustave Roussy. Gustave Roussy is active in numerous fields of expertise, reflecting the quality of the research conducted there and its international recognition.
Each year, nearly 20 million people worldwide are diagnosed with cancer, and 9 million die from it, according to the World Health Organization. These numbers are constantly increasing, as highlighted by a study published in September in The Lancet[1]. Researchers from the Global Burden of Disease programme report that between 1990 and 2023, the number of new cases worldwide more than doubled, while the number of deaths increased by 74%. They predict that by 2050, without new targeted funding measures, 30.5 million new cases will be reported each year, and 18.6 million deaths recorded.
It is therefore essential to reinforce cancer prevention programmes. To this end, the Early Detection and Prevention Task Force was established as a multidisciplinary European group affiliated with ESMO and led by Dr Suzette Delaloge, dedicated to conducting research and developing recommendations to guide cancer prevention efforts.
The first project from this working group, DRUGPREV, constitutes the first large-scale retrospective study dedicated to clinical trials of pharmacological cancer prevention, also known as chemoprevention. To this end, the researchers analysed around one hundred clinical trials conducted over more than four decades, in order to draw lessons and formulate recommendations for future prevention strategies.
Thousands of trials scrutinised
Over the past decades, primary cancer prevention strategies have mostly focused on reducing exposure to carcinogenic agents—such as tobacco, alcohol or certain infections. In contrast, very few drugs have been developed to prevent cancer onset (primary prevention) or treat precancerous lesions (secondary prevention), unlike the massive development of treatments for patients already affected by cancer.
According to the DRUGPREV team’s analysis, only 0.3% of all randomised clinical trials in oncology concerned the evaluation of a molecule aimed at preventing cancer.
To reach this finding, the researchers reviewed thousands of oncology trials conducted over several decades. They retained phase III trials, i.e., the last stage before potential marketing authorisation, evaluating a drug administered to healthy or at-risk individuals for preventive purposes. In total, 93 trials were identified, 91 of which were included in the statistical analysis. Among them, half demonstrated a significant effectiveness of the preventive medicinal intervention.
The results of DRUGPREV underline that the success of a trial largely depends on the robustness of prior scientific data, including preclinical and clinical mechanistic evidence. Large-scale international trials also stand out with a 96% success rate, while industry-sponsored studies show an 84% success rate.
Vaccination among the most effective preventions
The researchers then classified the trials according to the type of molecule evaluated. First observation: the vast majority of trials on vaccines against human papillomavirus (HPV) were highly effective in preventing cancers associated with this virus. Hormonal treatments, such as tamoxifen, also showed benefit, significantly reducing the risk of breast cancer in high-risk women. Non-steroidal anti-inflammatory drugs (NSAIDs), notably aspirin, demonstrated their ability to limit the formation of colorectal polyps in several studies. However, some studies also highlighted increased risks in elderly individuals, notably cardiovascular or haemorrhagic.
In contrast, trials evaluating vitamins and dietary supplements did not demonstrate effectiveness in cancer prevention. Among the 38 trials concerned, 29 were negative, and three even revealed serious adverse effects. This was notably the case for beta-carotene, associated with an increased risk of lung cancer, and combinations including vitamin E, linked to a higher risk of prostate cancer.
The need for solid scientific evidence
In general, few chemoprevention trials, even when positive, have led to routine clinical use. In many cases, the benefit/risk ratio of the tested molecules was not deemed sufficient to justify their routine use by regulatory authorities. To date, in the European Union, the HPV vaccine remains the only medicine authorised for preventive purposes against cancer.
The analysis further highlights that understanding the drug’s mechanism of action in carcinogenesis, before launching a trial, is the best predictor of success. The conclusions of DRUGPREV thus advocate for the development of molecules specifically designed for prevention, in addition to the repositioning of existing treatments. Finally, they call for the development of harmonised and pre-established methodological frameworks, essential to foster the emergence of new preventive strategies and their integration into clinical practice.
“Our analysis shows how much pharmacological cancer prevention remains a largely underexplored research field, especially compared to the effort invested in treatments. In forty years, barely 93 trials have been conducted, even as cancer mortality continues to rise worldwide. Acting only on risk factors will not be enough: we will also need to develop medicinal prevention approaches. We hope these results will help stimulate new research programmes in this still too-neglected area of oncology,” concludes Dr Alexandre Xu-Vuillard, oncologist at Gustave Roussy.
Abstract No. 2274O
Dissecting four decades of phase III randomised pharmacological interventions for primary cancer prevention to guide future developments - ESMO Early DEtection and PrevenTion Task Force.
Proffered paper session presented by Dr Alexandre Xu-Vuillard.
Saturday 18 October 2025 | 15:30.
[1]The global, regional, and national burden of cancer, 1990–2023, with forecasts to 2050: a systematic analysis for the Global Burden of Disease Study 2023 - Force, Lisa M et al. - The Lancet, Volume 0, Issue 0