Cabozantinib plus Atezolizumab in Advanced, Progressive Endocrine Malignancies: A Multicohort, Basket, Phase II Trial (CABATEN/GETNE-T1914).

Abstract

Multikinase inhibitors have shown efficacy in endocrine neoplasms, and synergism with immune checkpoint inhibitors has been noted in other tumors. This is a prospective, multicenter, open-label, Simon two-stage optimal design, phase II study including patients with advanced and refractory endocrine and neuroendocrine neoplasms in six cohorts: lung well-differentiated neuroendocrine tumors, anaplastic thyroid cancer (ATC), adrenocortical carcinoma (ACC), pheochromocytoma/paraganglioma (PPGL), well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NET), and grade 3 extrapulmonary neuroendocrine neoplasms. Patients received atezolizumab 1,200 mg intravenously every 3 weeks plus cabozantinib 40 mg/day orally until disease progression or unacceptable toxicity. The primary objective was the overall response rate (ORR) by RECIST 1.1. From October 2020 to December 2022, 93 patients were included. The ORR was 14.3% [95% confidence interval (CI), 1.8-42.8] in ATC (N = 14); 8.3% (95% CI, 1.0-27.0) in ACC (N = 24); 15.4% (95% CI, 1.9-45.5) in PPGL (N = 13), and 16.7% (95% CI, 4.7-37.4) in GEP-NET (N = 24). Lung well-differentiated neuroendocrine tumors and grade 3 extrapulmonary neuroendocrine neoplasms had no responses. The duration of response was 20.4 months in ATC, 13.1 months in ACC, 12.2 months in PPGL, and 15.8 months in GEP-NET. Survival rates at 12 months in ATC and ACC were 47.6% and 47.6%, respectively. No unexpected toxicity was observed. Cabozantinib and atezolizumab were safely administered and showed promising ORR, and preliminary long-term survival rates were observed in aggressive and pretreated ACC and ATC, which warrants further investigation.