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. 2019 Feb 28:12:1717-1728.
doi: 10.2147/OTT.S182259. eCollection 2019.

Everolimus for the treatment of advanced gastrointestinal or lung nonfunctional neuroendocrine tumors in East Asian patients: a subgroup analysis of the RADIANT-4 study

James C Yao  1 , Do-Youn Oh  2 , Jiaming Qian  3 , Young Suk Park  4 , Fabian Herbst  5 , Antonia Ridolfi  6 , Miguel Izquierdo  5 , Tetsuhide Ito  7 , Liqun Jia  8 , Izumi Komoto  9 , Virote Sriuranpong  10 , Yasuhiro Shimada  11
Affiliations

Everolimus for the treatment of advanced gastrointestinal or lung nonfunctional neuroendocrine tumors in East Asian patients: a subgroup analysis of the RADIANT-4 study

James C Yao et al. Onco Targets Ther. .

Abstract

Background: In RADIANT-4, everolimus showed an improvement of 7.1 months in median progression-free survival (PFS) vs placebo among patients with advanced, well-differentiated, nonfunctional neuroendocrine tumors (NETs) of gastrointestinal (GI) or lung origin. The present analysis focuses on the effect of everolimus on the East Asian-subgroup population of the RADIANT-4 study.

Methods: Patients were randomized to receive everolimus 10 mg/day or matching placebo. The primary end point was PFS (central review). Secondary end points were overall response rate, safety, and tolerability.

Results: Among 302 patients enrolled in RADIANT-4, 46 were included in the East Asian subgroup (everolimus, n=28; placebo, n=18) analysis. Everolimus was associated with an 82% reduction in the relative risk of disease progression or death (HR 0.18, 95% CI 0.09-0.38). The median PFS (central review) in this subgroup was 11.2 months with everolimus vs 3.1 months with placebo. Adverse events (AEs) occurred in all 28 patients treated with everolimus and ten patients receiving placebo. The majority of these AEs were grade 1 or 2. Most commonly reported ($30% of incidence) drug-related AEs of any grade included stomatitis (75%, n=21) and rash (43%, n=12) in the everolimus arm.

Conclusion: Everolimus demonstrated a clinically meaningful PFS benefit in the East Asian population. The safety findings were consistent with the known safety profile of everolimus. These results support the use of everolimus in the East Asian population with advanced, nonfunctional NETs of GI or lung origin.

Keywords: East Asian population; RADIANT-4; everolimus; mTOR inhibitors; neuroendocrine tumors.

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Conflict of interest statement

Disclosure The authors report the following types of declarations of interest: consultant/advisory relationship (C/A), employment (E), honoraria received (H), intellectual property rights/inventor/patent holder (IP), leadership position (L), ownership interest (OI), research funding (RF), speaker’s bureau (SB), and travel and accommodation expenses (TAE). JCY: Novartis (H, C/A), Ipsen (C/A). VS: Novartis (RF). YS: Novartis (H). FH: Novartis (E). AR: Novartis (E). MI: Novartis (E). The other authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Study design. Notes: aBased on prognostic level, grouped as: stratum A (better prognosis) – appendix, cecum, jejunum, ileum, duodenum, and NET of unknown primary; stratum B (worse prognosis) – lung, stomach, rectum, and colon except cecum. Abbreviations: NET, neuroendocrine tumor; SSA, somatostatin analogue; WHO PS, World Health Organization performance status.
Figure 2
Figure 2
Kaplan–Meier plot of progression-free survival. Notes: (A) East Asian subgroup; (B) overall population. Abbreviations: BSC, best supportive care; NA, not available.
Figure 3
Figure 3
Percentage changes from baseline in size of target lesion: central review (full-analysis set). Notes: (A) East Asian subgroup. (B) Overall population. Patients for whom the best percentage change in target lesion was not available and patients for whom the best percentage change in target lesions was contradicted by overall lesion response of unknown were excluded from the analysis. Abbreviation: BSC, best supportive care.
See this image and copyright information in PMC

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