Mitotane: a friend or a foe before cabozantinib treatment in adrenocortical cancer?
Mené sur 18 patients atteints d'un carcinome corticosurrénalien de stade avancé (durée médiane de suivi : 36,8 mois), cet essai de phase II évalue l'efficacité, du point de vue de la survie sans progression à 4 mois, et la toxicité du cabozantinib en monothérapie
Adrenocortical carcinoma is a rare cancer with a dismal prognosis, which affects 1–2 people per million annually, worldwide. 1 Because of the small number of patients within single centres and the scarcity of preclinical models until recently, 2 advancements in treatment options have been limited. Mitotane, a cell-specific adrenolytic, has been the mainstay of treatment, together with etoposide, doxorubicin, and cisplatin chemotherapy. 3 Early studies with tyrosine kinase inhibitors (TKIs) have not shown a strong signal of response in patients with adrenocortical carcinoma as monotherapy. 1 Cabozantinib is a multi-kinase inhibitor with major targeting of c-Met, AXL, RET, and VEGFR2. Anti-tumour activity with cabozantinib has been seen in preclinical studies in an adrenocortical carcinoma cell line and a xenograft mouse model. 4 A previous retrospective compilation across several institutions of 16 patients treated with cabozantinib with previous exposure to mitotane suggested it might be an effective monotherapy in advanced adrenocortical carcinoma after treatment failure. 5 In that study, recruited patients had low concentrations of mitotane at study entry. Three of 16 patients had a partial response, five patients had stable disease, and eight patients had progressive disease.
The Lancet Oncology 2023