Felix Megerle1, Wiebke Herrmann1, Wiebke Schloetelburg2, Cristina L Ronchi1,3, Alina Pulzer1, Marcus Quinkler4, Felix Beuschlein5,6, Stefanie Hahner1, Matthias Kroiss7, Martin Fassnacht1,7. 1. Department of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital Würzburg, University of Würzburg, Würzburg, Germany. 2. Department of Diagnostic and Interventional Radiology, University Hospital Würzburg, University of Würzburg, Würzburg, Germany. 3. Institute of Metabolism and System Research, University of Birmingham, Birmingham, United Kingdom. 4. Endocrinology in Charlottenburg, Berlin, Germany. 5. Department of Internal Medicine IV, Klinikum der Universität München, Munich, Germany. 6. Department of Endocrinology, Diabetology and Clinical Nutrition, Universitätsspital Zürich, Zurich, Switzerland. 7. Comprehensive Cancer Center Mainfranken, University of Würzburg, Würzburg, Germany.
Abstract
Context: Although mitotane is the only approved drug for the treatment of adrenocortical carcinoma (ACC), data on monotherapy in advanced disease are still scarce. Objective: To assess the efficacy of mitotane in advanced ACC in a contemporary setting and to identify predictive factors. Design and Setting: Multicenter cohort study of three German referral centers. Patients: One hundred twenty-seven patients with advanced ACC treated with mitotane monotherapy. Outcome Measures: Response Evaluation Criteria in Solid Tumors evaluation, progression-free survival (PFS) and overall survival (OS) by Kaplan-Meier method, and predictive factors by Cox regression. Results: Twenty-six patients (20.5%) experienced objective response, including three with complete remission. Overall, median PFS was 4.1 months (range 1.0 to 73) and median OS 18.5 months (range 1.3 to 220). Multivariate analysis indicated two main predictive factors: low tumor burden (<10 tumoral lesions), hazard ratio (HR) for progression of 0.51 (P = 0.002) and for death of 0.59 (P = 0.017); and initiation of mitotane at delayed advanced recurrence, HR 0.35(P < 0.001) and 0.34 (P < 0.001), respectively. Accordingly, 67% of patients with low tumor burden and mitotane initiation ≥360 days after primary diagnosis experienced a clinical benefit (stable disease >180 days). Patients who achieved mitotane levels >14 mg/L had significantly longer OS (HR 0.42; P = 0.003). Conclusions: At 20.5% the objective response rate was slightly lower than previously reported. However, >20% of patients experienced long-term disease control at >1 year. In general, patients with late diagnosis of advanced disease and low tumor burden might especially benefit from mitotane monotherapy, whereas patients with early advanced disease and high tumor burden are probably better candidates for combined therapy of mitotane and cytotoxic drugs.
Context: Although mitotane is the only approved drug for the treatment of adrenocortical carcinoma (ACC), data on monotherapy in advanced disease are still scarce. Objective: To assess the efficacy of mitotane in advanced ACC in a contemporary setting and to identify predictive factors. Design and Setting: Multicenter cohort study of three German referral centers. Patients: One hundred twenty-seven patients with advanced ACC treated with mitotane monotherapy. Outcome Measures: Response Evaluation Criteria in Solid Tumors evaluation, progression-free survival (PFS) and overall survival (OS) by Kaplan-Meier method, and predictive factors by Cox regression. Results: Twenty-six patients (20.5%) experienced objective response, including three with complete remission. Overall, median PFS was 4.1 months (range 1.0 to 73) and median OS 18.5 months (range 1.3 to 220). Multivariate analysis indicated two main predictive factors: low tumor burden (<10 tumoral lesions), hazard ratio (HR) for progression of 0.51 (P = 0.002) and for death of 0.59 (P = 0.017); and initiation of mitotane at delayed advanced recurrence, HR 0.35(P < 0.001) and 0.34 (P < 0.001), respectively. Accordingly, 67% of patients with low tumor burden and mitotane initiation ≥360 days after primary diagnosis experienced a clinical benefit (stable disease >180 days). Patients who achieved mitotane levels >14 mg/L had significantly longer OS (HR 0.42; P = 0.003). Conclusions: At 20.5% the objective response rate was slightly lower than previously reported. However, >20% of patients experienced long-term disease control at >1 year. In general, patients with late diagnosis of advanced disease and low tumor burden might especially benefit from mitotane monotherapy, whereas patients with early advanced disease and high tumor burden are probably better candidates for combined therapy of mitotane and cytotoxic drugs.
Authors: Nikita Pozdeyev; Lauren Fishbein; Laurie M Gay; Ethan S Sokol; Ryan Hartmaier; Jeffrey S Ross; Sourat Darabi; Michael J Demeure; Adwitiya Kar; Lindsey J Foust; Katrina Koc; Daniel W Bowles; Stephen Leong; Margaret E Wierman; Katja Kiseljak-Vassiliades Journal: Endocr Relat Cancer Date: 2021-08-16 Impact factor: 5.900
Authors: Matthias Kroiss; Felix Megerle; Max Kurlbaum; Sebastian Zimmermann; Julia Wendler; Camilo Jimenez; Constantin Lapa; Marcus Quinkler; Oliver Scherf-Clavel; Mouhammed Amir Habra; Martin Fassnacht Journal: J Clin Endocrinol Metab Date: 2020-05-01 Impact factor: 5.958