Efficacy of RAD001 (everolimus) and octreotide LAR in advanced low- to intermediate-grade neuroendocrine tumors: Results of a phase II study

James C. Yao, Alexandria T. Phan, David Z. Chang, Robert A. Wolff, Kenneth Hess, Sanjay Gupta, Carmen Jacobs, Jeannette E. Mares, Andrea N. Landgraf, Asif Rashid, Funda Meric-Bernstam

Research output: Contribution to journalArticle

503 Scopus citations

Abstract

Purpose: Evaluate the activity of everolimus (RAD001) in combination with octreotide long-acting repeatable (LAR) in patients with advanced low- to intermediate-grade neuroendocrine tumors. Methods: Treatment consisted of RAD001 5 mg/d (30 patients) or 10 mg/d (30 patients) and octreotide LAR 30 mg every 28 days. Thirty carcinoid and 30 islet cell patients were enrolled. Results Intent-to-treat response rate was 20%. Per protocol, there were 13 with partial responses (22%), 42 with stable disease (SD; 70%), and five patients with progressive disease (8%). Overall median progression-free survival (PFS) was 60 weeks. Median PFS for patients with known SD at entry was longer than for those who had progressive disease (74 v 50 weeks; P <.01). Median overall survival has not been reached. One-, 2-, and 3-year survival rates were 83%, 81 %, and 78%, respectively. Among 37 patients with elevated chromogranin A, 26 (70%) achieved normalization or more than 50% reduction. Most common toxicity was mild aphthous ulceration. Grade 3/4 toxicities occurring in ≥ 10% of patients included hypophosphatemia (11 %), fatigue (11 %), and diarrhea (11 %). Treatment was associated with a dose-dependent rise in lactate dehydrogenase (LDH). Those with lower than 109 U/L rise in LDH at week 4 had shorter PFS (38 v69 weeks; P = .01). Treatment was also associated with a decrease in proliferation marker Ki-67 among patients who underwent optional paired pre- and post-treatment biopsy (P = .04). Conclusion RAD001 at 5 or 10 mg/d was well tolerated in combination with octreotide LAR, with promising antitumor activity. Confirmatory studies are ongoing.

Original languageEnglish (US)
Pages (from-to)4311-4318
Number of pages8
JournalJournal of Clinical Oncology
Volume26
Issue number26
DOIs
StatePublished - Sep 10 2008

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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