Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Oct 16:10:5013-5030.
doi: 10.2147/OTT.S142087. eCollection 2017.

Impact of prior therapies on everolimus activity: an exploratory analysis of RADIANT-4

Roberto Buzzoni  1 , Carlo Carnaghi  2 , Jonathan Strosberg  3 , Nicola Fazio  4 , Simron Singh  5 , Fabian Herbst  6 , Antonia Ridolfi  7 , Marianne E Pavel  8 , Edward M Wolin  9 , Juan W Valle  10 , Do-Youn Oh  11 , James C Yao  12 , Rodney Pommier  13
Affiliations

Impact of prior therapies on everolimus activity: an exploratory analysis of RADIANT-4

Roberto Buzzoni et al. Onco Targets Ther. .

Abstract

Background: Recently, everolimus was shown to improve median progression-free survival (PFS) by 7.1 months in patients with advanced, progressive, well-differentiated, nonfunctional neuroendocrine tumors (NET) of lung or gastrointestinal (GI) tract compared with placebo (HR, 0.48; 95% CI, 0.35-0.67; P<0.00001) in the Phase III, RADIANT-4 study. This post hoc analysis evaluates the impact of prior therapies (somatostatin analogs [SSA], chemotherapy, and radiotherapy) on everolimus activity.

Trial registration: ClinicalTrials.gov identifier: NCT01524783.

Patients and methods: Patients were randomized (2:1) to everolimus 10 mg/day or placebo, both with best supportive care. Subgroups of patients who received prior SSA, chemotherapy, or radiotherapy (including peptide receptor radionuclide therapy) were analyzed and reported.

Results: A total of 302 patients were enrolled, of whom, 163 (54%) had any prior SSA use (mostly for tumor control), 77 (25%) received chemotherapy, and 63 (21%) were previously exposed to radiotherapy. Patients who received everolimus had longer median PFS compared with placebo, regardless of previous SSA (with SSA: 11.1 vs 4.5 months [HR, 0.56 {95% CI, 0.37-0.85}]; without SSA: 9.5 vs 3.7 months [0.57 {0.36-0.89}]), chemotherapy (with chemotherapy: 9.2 vs 2.1 months [0.35 {0.19-0.64}]; without chemotherapy: 11.2 vs 5.4 months [0.60 {0.42-0.86}]), or radiotherapy (with radiotherapy: 9.2 vs 3.0 months [0.47 {0.24-0.94}]; without radiotherapy: 11 vs 5.1 months [0.59 {0.42-0.83}]) exposure. The most frequent drug-related adverse events included stomatitis (59%-65%), fatigue (27%-35%), and diarrhea (24%-34%) among the subgroups.

Conclusion: These results suggest that everolimus improves PFS in patients with advanced, progressive lung or GI NET, regardless of prior therapies. Safety findings were consistent with the known safety profile of everolimus in NET.

Keywords: PRRT; chemotherapy; neuroendocrine tumors; progression-free survival; somatostatin analogs.

PubMed Disclaimer

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). Roberto Buzzoni: Italfarmaco, Novartis, Otsuka (RF); Ipsen, Italfarmaco, Novartis (TAE); Jonathan Strosberg: Novartis (H); Ipsen, Lexicon, Novartis (C/A); Novartis, Pfizer (RF); Bayer, Genentech (SB); Nicola Fazio: Ipsen, Novartis (H); Ipsen, Lexicon, Novartis, Italfarmaco (C/A); Novartis (RF); Ipsen, Novartis (TAE); Simron Singh: Novartis (H, C/A, TAE, RF); Fabian Herbst: Novartis (E, OI); Antonia Ridolfi: Novartis (E); Marianne E Pavel: Ipsen, Lexicon, Novartis, Pfizer (H); Ipsen, Lexicon, Novartis, Pfizer (C/A); Novartis (RF); Ipsen, Novartis (TAE); Edward M Wolin: Celgene, Ipsen, Novartis (C/A); Juan W Valle: Novartis (H, C/A, RF); James C Yao: Ipsen, Lexicon, Novartis (C/A); Novartis (RF); Rodney Pommier: Novartis, Pfizer, Ipsen, Lexicon (C/A); Novartis, Ipsen, Lexicon (TAE). The other authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Progression-free survival by central review (full analysis set). Notes: Kaplan–Meier curves are shown for progression-free survival as assessed by central radiology review for both treatment arms (everolimus and placebo) in the patients who received (A) prior SSA, (B) no prior SSA, (C) prior chemotherapy, (D) no prior chemotherapy, (E) prior radiotherapy, and (F) no prior radiotherapy. The HRs in subgroups are obtained from unstratified Cox proportional hazards model. Abbreviations: CI, confidence interval; HR, hazard ratio; SSA, somatostatin analogs.
Figure 2
Figure 2
Percentage change from baseline in size of target lesion, central review (full analysis set). Notes: The plot shows the best percentage change from baseline in the size of the target lesion (ie, the best response in each patient) in the everolimus arm (left) and placebo arm (right) in the patients who received (A) prior SSA, (B) no prior SSA, (C) prior chemotherapy, (D) no prior chemotherapy, (E) prior radiotherapy, and (F) no prior radiotherapy. Abbreviations: PD, progressive disease; SSA, somatostatin analogs.
Figure 2
Figure 2
Percentage change from baseline in size of target lesion, central review (full analysis set). Notes: The plot shows the best percentage change from baseline in the size of the target lesion (ie, the best response in each patient) in the everolimus arm (left) and placebo arm (right) in the patients who received (A) prior SSA, (B) no prior SSA, (C) prior chemotherapy, (D) no prior chemotherapy, (E) prior radiotherapy, and (F) no prior radiotherapy. Abbreviations: PD, progressive disease; SSA, somatostatin analogs.
See this image and copyright information in PMC

References

    1. Maggard MA, O’Connell JB, Ko CY. Updated population-based review of carcinoid tumors. Ann Surg. 2004;240(1):117–122. - PMC - PubMed
    1. Yao JC, Hassan M, Phan A, et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008;26(18):3063–3072. - PubMed
    1. Shen C, Dasari A, Zhao B, et al. Incidence and prevalence of neuroendocrine tumors in the United States 1973–2012. abstr 121 presented at NANETS 2016.
    1. Vinik AI, Woltering EA, Warner RR, et al. NANETS consensus guidelines for the diagnosis of neuroendocrine tumor. Pancreas. 2010;39(6):713–734. - PubMed
    1. Kunz PL, Reidy-Lagunes D, Anthony LB, et al. Consensus guidelines for the management and treatment of neuroendocrine tumors. Pancreas. 2013;42(4):557–577. - PMC - PubMed

Associated data