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Cabozantinib plus Atezolizumab in Advanced, Progressive Endocrine Malignancies: A Multicohort, Basket, Phase II Trial
Jaume Capdevila1, Jorge Hernando1, Javier Molina-Cerrillo2
1Medical Oncology Department, Vall Hebron University Hospital, Vall Hebron Institute of Oncology (VHIO), Barcelona, Spain.
Purpose:
Multikinase inhibitors have shown efficacy in endocrine neoplasms, and synergism with immune checkpoint inhibitors has been noted in other tumors.
Patients And Methods:
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.
Results:
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.
Conclusions:
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.
Insights
This phase II study evaluated atezolizumab plus cabozantinib in advanced endocrine and neuroendocrine neoplasms. The combination showed promising overall response rates and survival in aggressive adrenocortical carcinoma and anaplastic thyroid cancer.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Multikinase inhibitors demonstrate efficacy in endocrine neoplasms.
- Synergistic effects of multikinase inhibitors and immune checkpoint inhibitors are observed in various cancers.
Purpose of the Study:
- To evaluate the efficacy and safety of atezolizumab plus cabozantinib in patients with advanced and refractory endocrine and neuroendocrine neoplasms.
- To determine the overall response rate (ORR) as the primary endpoint.
Main Methods:
- Prospective, multicenter, open-label, phase II study with a Simon two-stage optimal design.
- Six patient cohorts: lung well-differentiated neuroendocrine tumors, anaplastic thyroid cancer (ATC), adrenocortical carcinoma (ACC), pheochromocytoma/paraganglioma (PPGL), gastroenteropancreatic neuroendocrine tumors (GEP-NET), and grade 3 extrapulmonary neuroendocrine neoplasms.
- Treatment: Atezolizumab 1,200 mg IV every 3 weeks + cabozantinib 40 mg/day orally until disease progression or toxicity.
Main Results:
- Overall response rates (ORR) were observed in ATC (14.3%), ACC (8.3%), PPGL (15.4%), and GEP-NET (16.7%).
- No responses were noted in lung well-differentiated neuroendocrine tumors and grade 3 extrapulmonary neuroendocrine neoplasms.
- Preliminary 12-month survival rates were 47.6% for both ATC and ACC. Duration of response varied across cohorts. No unexpected toxicities were reported.
Conclusions:
- Cabozantinib and atezolizumab combination therapy is safe and demonstrates promising ORR in advanced endocrine and neuroendocrine neoplasms.
- Preliminary long-term survival data in aggressive, pretreated ACC and ATC suggest potential benefit, warranting further investigation.
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