The ADIUVO-2 randomized trial – a clinical and molecular enterprise to cure ACC
Joakim Crona · Martin Fassnacht · Mouhammed Amir Habra · Rossella Libé · Massimo Terzolo · Alfredo Berruti (Uppsala University Hospital · University Hospital of Würzburg · University of Texas · Cochin Hospital · University of Turin · University of Brescia)
Disease information: Adrenocortical carcinoma (ACC) is a very rare cancer arising in the adrenal glands. Some patients have a low risk of disease recurrence after surgery. Others, those with high-risk disease, face a much greater chance of recurrence and worse outcomes. Forthese high-risk patients, better treatment and earlier detection methods could significantly
improve cure rates and survival.
Background of the research project: In clinical practice, mitotane is an oral medication commonly given after surgical resection of ACC to improve survival and reduce risk of disease recurrence. In patients with ACC who were at high risk for recurrence, adjuvant chemotherapy was associated with beneficial clinical outcomes based on retrospective data analysis. While mitotane is the only approved drug in ACC, it is associated with low efficacy rates in ACC. Furthermore, mitotane has lag time and delayed anti-cancer effect for at least 2-3 months until sufficiently high blood levels are achieved. Thus, the main rationale for this study is to use chemotherapy in the first few months of mitotane use to cover this anticipated delay in mitotane action. However, the role of mitotane or mitotane combination with chemotherapy have not been validated prospectively. To test the efficacy of mitotane as compared with mitotane plus chemotherapy, an international group of researchers launched a major clinical trial: ADIUVO-2. This trial shows potential, but it completion is jeopardized by the lack of funding.
Key objectives of the research project: This study is comparing two adjuvant approaches for high-risk ACC patients after surgery: Treatment with (A) mitotane alone for 2 years and (B) treatment with mitotane for 2 years combined with chemotherapy drugs (etoposide and cisplatin) in the first 3 months of therapy. The trial also aims to enable future research on whether new laboratory methods can detect ACC recurrences earlier and help personalize treatment. ADIUVO2 will collect blood to analyses hormone byproducts and to detect pieces of cancer DNA, tumor tissues to perform molecular analyses and radiology scans to allow for advanced computational analyses.
Expected results: The study aimsto recruit a total of 240 patients over the next few years, with help from more participating hospitals and additional funding. The results will demonstrate, which adjuvant strategy is superior in patients with high-risk AC. In addition, by collecting and analyzing blood, tumor samples, and imaging data, ADIUVO-2 will contribute to research on how to better predict who will benefit from which treatment and if we can detect relapses sooner than with standard scans. With the recent support from several European countries, ADIUVO-2 has regained momentum. As of mid 2025, 54 patients have joined the study.
Knowledge utilization and impact on healthcare: Ultimately, ADIUVO-2 is not just testing if chemotherapy can increase the cure rate aftersurgery of high-risk tumors. With its exploratory analyses it’s paving the way for more personalized care for patients with ACC. Its findings will help shape the next major trial, ADIUVO-3, which could bring even better outcomesfor people
facing this challenging disease.