Cabozantinib für fortgeschrittenes Nebennierenrindenkarzinom – ASCO-Beitrag

Vollstaendiger Artikelinhalt

In a single-center phase II trial reported in The Lancet Oncology, Campbell et al found that cabozantinib monotherapy showed activity in adult patients with advanced adrenocortical carcinoma. In the trial, 18 patients enrolled at The University of Texas MD Anderson Cancer Center between March 2018 and May 2021 were treated with cabozantinib at 60 mg daily. Patients were not candidates for curative surgery. Concomitant mitotane was not permitted; patients who had received mitotane within 6 months of study participation were required to have a mitotane serum level of < 2 mg/L. Among the 18 patients, 11 (61%) had undergone prior adrenal surgery and 16 (89%) had received prior systemic therapy. The primary endpoint of the trial was 4-month progression-free survival. Median follow-up was 36.8 months (interquartile range = 30.2–50.3 months). A total of 13 patients (72.2%, 95% confidence interval = 46.5%–90.3%) had progression-free survival at 4 months. Median progression-free survival was 6 months (95% CI = 4.3 months to not reached). Median overall survival was 24 months (95% CI = 15.6 months to not reached). Objective response was observed in 2 patients (11%, 95% CI = 1.4%–35.0%) and objective response or stable disease was observed in 14 (78%, 95% CI = 52%–94%). Treatment-related grade 3 or 4 adverse events occurred in 11 (61%) of 18 patients, most commonly hypertension (n = 3,17%, 1 grade 4), lipase elevation (n = 3,17%, all grade 3), elevated γ-glutamyl transferase (n = 2,11%, both grade 3), elevated alanine aminotransferase (n = 2,11%, both grade 3), and hypophosphatemia (n = 2,11%, both grade 3). Dose reduction from 60 mg/day to 40 mg/day to manage adverse events occurred in 11 patients (61%), with 3 requiring a further reduction to 20 mg/day. No treatment-related deaths were reported. The investigators concluded, “Cabozantinib in advanced adrenocortical carcinoma showed promising efficacy with a manageable and anticipated safety profile. Further prospective studies with cabozantinib alone and in combination with immune checkpoint therapy are ongoing. ” Matthew T. Campbell, MD, of the Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, is the corresponding author for The Lancet Oncology article. Disclosure: The study was funded by Exelixis. For full disclosures of the study authors, visit thelancet. com.