A pilot study of everolimus and radiation for neuroendocrine liver metastases.

Abstract

Liver metastases are common in patients with neuroendocrine tumors. For patients, management must balance disease control with consideration of toxicity, given limited treatment options. Everolimus has demonstrated effectiveness in neuroendocrine neoplasms. Given emerging data of a synergistic effect with radiation therapy, we evaluated combined Everolimus and radiation for neuroendocrine liver metastases. This single-arm, single centre prospective pilot study evaluated the safety and efficacy of combined everolimus and radiotherapy for well-differentiated neuroendocrine liver metastases. Patients with unresectable liver metastases received everolimus for 30 days, followed by concurrent everolimus and liver radiotherapy, then a further 14 days of everolimus. Tolerability was evaluated using the CTCAE v.4.03. Individual metastasis response rate and local control were measured by RECIST v1.1. Overall survival, progression-free survival and freedom from change in systemic therapy were estimated by the Kaplan-Meier method. 40 metastases were treated in 14 patients. No Grade 3 or higher toxicities were identified in the concurrent treatment phase; 8 grade 2 toxicity and 1 patient develped grade 3 toxicity in the post-radiation phase. Overall response rate was 38%. One and 2-year local control was 97% and 71%. Median progression free survival was 12 months. One and 2-year overall survival were 100% and 92%. In conclusion, combined everolimus and radiation is well-tolerated for neuroendocrine liver metastases and is associated with excellent local control. The approach of selective local ablation of oligometastatic or oligoprogressive disease warrants further evaluation in this patient population.