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. 2013;18(1):46-53.
doi: 10.1634/theoncologist.2012-0263. Epub 2012 Dec 21.

Everolimus plus octreotide long-acting repeatable in patients with colorectal neuroendocrine tumors: a subgroup analysis of the phase III RADIANT-2 study

Daniel Castellano  1 , Emilio Bajetta, Ashok Panneerselvam, Stephen Saletan, Walter Kocha, Thomas O'Dorisio, Lowell B Anthony, Timothy Hobday; RADIANT-2 Study Group
Affiliations

Everolimus plus octreotide long-acting repeatable in patients with colorectal neuroendocrine tumors: a subgroup analysis of the phase III RADIANT-2 study

Daniel Castellano et al. Oncologist. 2013.

Abstract

Introduction: The incidence of colorectal neuroendocrine tumors (NETs) is increasing, and patients with this disease have particularly poor prognoses. Treatment options are limited, and survival times have not improved in the past decade.

Methods: A post hoc analysis of the efficacy and tolerability of everolimus plus octreotide long-acting repeatable (LAR) was conducted in patients with colorectal NETs enrolled in the phase III RAD001 in Advanced Neuroendocrine Tumors, Second Trial (RADIANT-2) study. The primary endpoint (progression-free survival [PFS]), secondary endpoints (including objective response rate), and safety were assessed.

Results: Patients with colorectal NETs receiving everolimus plus octreotide LAR had a significantly longer median PFS (29.9 months; n = 19) than did those receiving placebo plus octreotide LAR (6.6 months; n = 20). Everolimus plus octreotide LAR treatment also significantly reduced the risk for disease progression (hazard ratio: 0.34; 95% confidence interval: 0.13-0.89; p = .011). Although no objective responses were observed, tumor shrinkage was more frequently noted in the everolimus plus octreotide LAR arm than in the placebo plus octreotide LAR arm (67% vs. 37%, respectively). The combination of everolimus plus octreotide LAR was generally well tolerated by patients with colorectal NETs; rash and stomatitis were the most commonly reported adverse events.

Conclusions: Everolimus plus octreotide LAR treatment had significant benefits and improved outcomes for patients with advanced colorectal NETs compared with placebo plus octreotide LAR treatment. Results of this exploratory analysis are consistent with those reported from the RADIANT-2 primary analysis. These findings support additional investigations of everolimus plus octreotide LAR in patients with colorectal NETs.

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Conflict of interest statement

Disclosures of potential conflicts of interest may be found at the end of this article.

Figures

Figure 1.
Figure 1.
RADIANT-2 study design for patients with colorectal neuroendocrine tumors. Abbreviations: LAR, long-acting repeatable; NET, neuroendocrine tumors.
Figure 2.
Figure 2.
RADIANT-2 CONSORT diagram. Reprinted from Pavel ME, Hainsworth JD, Baudin E et al. Everolimus plus octreotide long-acting repeatable for the treatment of advanced neuroendocrine tumours associated with carcinoid syndrome (RADIANT 2): A randomised, placebo-controlled, phase 3 study. Lancet 2011;378:2005–2012 [24], with permission from Elsevier.
Figure 3.
Figure 3.
Kaplan-Meier plot of progression-free survival times in patients with colorectal neuroendocrine tumors per adjudicated central radiology review. Hazard ratio is obtained from unadjusted Cox model. Both treatments are combined with octreotide long-acting repeatable. p values were obtained from one-sided log-rank tests. Abbreviations: CI, confidence interval; HR, hazard ratio; LAR, long-acting repeatable.
Figure 4.
Figure 4.
Best percentage change from baseline in target lesion size of colorectal tumors. Abbreviation: LAR, long-acting repeatable.
See this image and copyright information in PMC

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