Phase II study of RAD001 (everolimus) and depot octreotide (sandostatin LAR) in advanced low grade neuroendocrine carcinoma (LGN

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Phase II study of RAD001 (everolimus) and depot octreotide
(sandostatin LAR) in advanced low grade neuroendocrine carcinoma

2007 ASCO Annual Meeting

Abstract No:
Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 4503
J. C. Yao, A. Phan, D. Z. Chang, R. A. Wolff, C. Jacobs, J. E. Mares, S. Gupta, F. Meric-Bernstam, A. Rashid
Effective systemic therapy for advanced LGNET is lacking. Mutations
involving the mTOR pathway including TSC2, NF-1, and vHL are associated
with development of LGNET. mTOR also mediate signaling downstream of
IGF1 and VEGF. RAD001 is a novel oral mTOR inhibitor. Octreotide has
been described to inhibit VEGF and IGF1 production in solid tumors.
Patients (pts) received depot octreotide 30 mg q28 days, and RAD001 5
(pts 1-30) or 10 mg (pts 31-60) po daily. Response was evaluated every
12 weeks (wks).
Results: 30 carcinoid (C) and 30 islet cell (I)
patients (pts) were enrolled between 2/05-7/06. 38 pts (23 C, 15 I) had
prior octreotide. By RECIST criteria, there were 10 PR (17%), 45 SD
(75%) (15 pts had > 15% reduction), 5 PD (8%). The response rates
within C, and I groups were 13% and 20%. The response rates within the
5 mg and 10 mg groups were 13% and 20% respectively. Of 39 pts with PD
prior to study entry, there were 7 (18%) PR, 27 (69%) SD (9 pts had
> 15% reduction), 5 (13%) PD. PFS rate at 24 wks was 86%. The median
PFS duration is 59 wks. The median PFS duration among the C and I
groups were 69 and 39 wks. Among the 39 pts with progression at study
entry, the median PFS duration was 38 wks. Of 24 pts with elevated
chromogranin A at entry, 19 (56%) had > 50% reduction. Treatment was
well tolerated. The most common toxicity was mild aphthous ulceration.
CTC G3/4 toxicities included: thrombocytopenia (3), neutropenia (3),
hypophosphatemia (5), hyperglycemia (4), hypoglycemia (2), hypokalemia
(2), fatigue (6), diarrhea (6), aphthous ulcer (5), rash (3), and 1
each of anemia, hypertriglyceridemia, bilirubin, AST/ALT, pain, nausea,
nail, dysgeusia, pneumonitis.
Conclusions: RAD001 at 5 or 10 mg
daily was well tolerated in combination with octreotide. Promising
anti-tumor activity has been observed. The RADIANT (RAD001 In Advanced
Neuroendocrine Tumors) trials are underway to evaluate RAD001 in larger
patient groups.