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

Buzzoni R, Carnaghi C, Strosberg J, Fazio N, Singh S, Herbst F, Ridolfi A, Pavel ME, Wolin EM, Valle JW, Oh DY, Yao JC, Pommier R (2017)

Publication Type: Journal article

Publication year: 2017

Journal

Oncotargets and Therapy Dove Medical Press

Book Volume: 10

Pages Range: 5013-5030

DOI: 10.2147/OTT.S142087

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.

Authors with CRIS profile

Marianne Ellen Pavel Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology

Involved external institutions

Fondazione IRCCS: Istituto Nazionale dei Tumori IT Italy (IT) Istituto Clinico Humanitas IT Italy (IT) H. Lee Moffitt Cancer Center & Research Institute US United States (USA) (US) European Institute of Oncology / Istituto Europeo di Oncologia (IEO) IT Italy (IT) Sunnybrook Health Sciences Centre CA Canada (CA) Novartis AG CH Switzerland (CH) Novartis Pharma S.A.S. FR France (FR) Montefiore Medical Center US United States (USA) (US) University of Manchester GB United Kingdom (GB) Seoul National University (SNU) / 서울대학교 KR Korea, Republic of (KR) University of Texas MD Anderson Cancer Center US United States (USA) (US) Oregon Health and Science University (OSHU) US United States (USA) (US)

How to cite

APA:

Buzzoni, R., Carnaghi, C., Strosberg, J., Fazio, N., Singh, S., Herbst, F.,... Pommier, R. (2017). Impact of prior therapies on everolimus activity: an exploratory analysis of RADIANT-4. Oncotargets and Therapy, 10, 5013-5030. https://doi.org/10.2147/OTT.S142087

MLA:

Buzzoni, Roberto, et al. "Impact of prior therapies on everolimus activity: an exploratory analysis of RADIANT-4." Oncotargets and Therapy 10 (2017): 5013-5030.

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