Efficacy of RAD001 (everolimus) and octreotide LAR in advanced low- to intermediate-grade neuroendocrine tumors: results of a ..

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J Clin Oncol. 2008 Sep 10;26(26):4311-8.

Erratum in:
J Clin Oncol. 2008 Dec 1;26(34)5660..

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

Yao JC, Phan AT, Chang DZ, Wolff RA, Hess K, Gupta S, Jacobs C, Mares JE, Landgraf AN, Rashid A, Meric-Bernstam F.
of Gastrointestinal Medical Oncology, Unit 426, The University of Texas
MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.

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 >or= 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 v 69 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).
RAD001 at 5 or 10 mg/d was well tolerated in combination with
octreotide LAR, with promising antitumor activity. Confirmatory studies
are ongoing.