Phase II study of cabazitaxel as second-third line treatment in patients with metastatic adrenocortical carcinoma
Marta Laganà, Salvatore Grisanti, Roberta Ambrosini, Deborah Cosentini, Andrea Abate, Manuel Zamparini, Vittorio Ferrari, Alessandra Gianoncelli, Antonella Turla, Letizia Canu, Massimo Terzolo, Guido Alberto Massimo Tiberio, Sandra Sigala, Alfredo Berruti
Abstract
•Cabazitaxel is well tolerated but poorly active as second/third-line treatment in patients with advanced ACC.•Combining RECIST and Choi criteria could be of value in the assessment of disease response to chemotherapy in ACC patients.•Older age, elevated cortisol and LDH blood level correlate with a greater risk of death in multivariate analysis. BackgroundAdrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a poor prognosis. No efficacious treatment options are currently available for patients with advanced metastatic disease with disease progression to standard etoposide, doxorubicin, cisplatin and mitotane (EDP-M) therapy. We assessed the activity and tolerability of cabazitaxel as a second/third-line approach in metastatic ACC.Patients and methodsPatients included in this single-center, phase II study (ClinicalTrials.gov identifier NCT03257891) had disease progression to a cisplatin-containing regimen (such as EDP) plus mitotane, plus/minus a further chemotherapy line. Cabazitaxel was administered intravenously at 25 mg/m2 on day 1 of a 21-day cycle, for a maximum of six cycles. The primary endpoint was a disease control rate after 4 months.ResultsFrom March 2018 to September 2019, 25 eligible patients were enrolled. A disease control rate after 4 months was obtained in six patients (24%). No patients attained a disease response according to RECIST 1.1, 9 patients (36%) had stable disease and 16 patients (64%) progressive disease. Median progression-free survival and overall survival were 1.5 months (range 0.3-7 months) and 6 months (range 1-22.2 months), respectively. Cabazitaxel therapy was well tolerated and only three (12%) patients developed grade 3 toxicity which were nausea in one patient (4%) and anemia in two patients (8%).ConclusionsCabazitaxel has a manageable toxicity profile but is poorly active as second/third-line treatment in advanced ACC patients. These results do not support further evaluation of cabazitaxel in this setting. Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a poor prognosis. No efficacious treatment options are currently available for patients with advanced metastatic disease with disease progression to standard etoposide, doxorubicin, cisplatin and mitotane (EDP-M) therapy. We assessed the activity and tolerability of cabazitaxel as a second/third-line approach in metastatic ACC. Patients included in this single-center, phase II study (ClinicalTrials.gov identifier NCT03257891) had disease progression to a cisplatin-containing regimen (such as EDP) plus mitotane, plus/minus a further chemotherapy line. Cabazitaxel was administered intravenously at 25 mg/m2 on day 1 of a 21-day cycle, for a maximum of six cycles. The primary endpoint was a disease control rate after 4 months. From March 2018 to September 2019, 25 eligible patients were enrolled. A disease control rate after 4 months was obtained in six patients (24%). No patients attained a disease response according to RECIST 1.1, 9 patients (36%) had stable disease and 16 patients (64%) progressive disease. Median progression-free survival and overall survival were 1.5 months (range 0.3-7 months) and 6 months (range 1-22.2 months), respectively. Cabazitaxel therapy was well tolerated and only three (12%) patients developed grade 3 toxicity which were nausea in one patient (4%) and anemia in two patients (8%). Cabazitaxel has a manageable toxicity profile but is poorly active as second/third-line treatment in advanced ACC patients. These results do not support further evaluation of cabazitaxel in this setting.