New findings do not support the routine use of adjuvant mitotane for patients with adrenocortical carcinoma (ACC) who are at low or intermediate risk of relapse after surgery, according to a presentation at the ASCO Genitourinary Cancers Symposium 2022.
The findings come from the ADIUVO trial (ClinicalTrials.gov Identifier: NCT00777244), the first randomized study of adjuvant mitotane in patients with ACC.
Although surgery is the mainstay of ACC treatment, roughly 40% to 70% of patients relapse after surgery, so there is a “strong rationale” for adjuvant therapy in this setting, said Alfredo Berruti, MD, of the University of Brescia in Italy, when presenting results from ADIUVO at the meeting.
International guidelines recommend adjuvant mitotane for ACC patients with a high risk of relapse, but the recommendation for low-risk patients is to make treatment decisions on a case-by-case basis, Dr Berruti noted.
The ADIUVO study enrolled 91 patients with ACC and a low or intermediate risk of relapse after surgery. Investigators randomly assigned 46 patients to observation and 45 patients to receive adjuvant mitotane for at least 2 years, with a target plasma level of 14-20 mg/L.
Baseline characteristics were well balanced between the arms. The primary endpoint was relapse-free survival.
At a median follow-up of 48 months, 8 patients (18%) in the mitotane arm and 11 (24%) in the observation arm experienced disease relapse. In addition, 2 patients (4%) in the mitotane arm and 5 (11%) in the observation arm died.
The 5-year relapse-free survival rate was 79% in the mitotane arm and 75% in the observation arm (hazard ratio [HR], 0.74; 95% CI, 0.30-1.85; P =.52). The 5-year overall survival rates were 95% and 86%, respectively (HR, 0.46; 95% CI, 0.08-1.92; P =.27).
Based on these results, Dr Berruti said, the investigators cannot recommend adjuvant mitotane for this patient population.
He pointed out, however, that the observed effect of adjuvant mitotane (a 26% reduction in relapse risk) “might be, in theory, of clinical relevance, although the large confidence intervals of the estimates due to the small numbers of events prevent any firm conclusion.”
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
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Berruti A, Fassnacht M, Libè R, et al. First randomized trial on adjuvant mitotane in adrenocortical carcinoma patients: The Adiuvo study. Presented at ASCO GU 2022; February 17-19, 2022. Abstract 1.