| General information |
| Database: | DB00982 |
| Objective: | Effective systemic therapies for patients with advanced, progressive neuroendocrine tumours of the lung or gastrointestinal tract are scarce. they aimed to assess the efficacy and safety of everolimus compared with placebo in this patient population. |
| Authors: | Yao JC, et al |
| Title: | Everolimus for the treatment of advanced, nonfunctional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT4): a randomised, placebocontrolled, phase 3 study. |
| Journal: | Lancet. |
| Year: | 2016 |
| PMID: | 26703889 |
| Trial Design |
| Clinical Trial Id: | NCT01524783 |
| Agent: | everolimus
|
| Target: | Serine/threonineprotein kinase mTOR
|
| Cancer Type: | neuroendocrine tumour |
| Cancer Subtype: | advanced, nonfunctional neuroendocrine tumours of the lung or gastrointestinal tract |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a randomised, placebocontrolled, phase III study. |
| Key Patients Feature: | adult patients (aged more than and equal to 18 years) with advanced, progressive, welldifferentiated, nonfunctional neuroendocrine tumours of lung or gastrointestinal origin were enrolled from 97 centres in 25 countries worldwide |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | everolimus versus placebo |
| Treatment Info: | Eligible patients were randomly assigned in a 2:1 ratio by an interactive voice response system to receive everolimus 10 mg per day orally or identical placebo, both with supportive care. |
| Primary End Point: | progression free survival assessed by central radiology review, analysed by intention to treat. |
| Secondary End Point: | Overall survival |
| Patients Number: | 302 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 2% in everolimus and 1% in placebo. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 11.0 months (95% CI 9.213.3) in the everolimus group and 3.9 months (3.67.4) in the placebo group. |
| Median OS A vs. C: | 23.7 months (95% CI 17.6-27.3) in the everolimus group and 16.5 months (9.0-21.0) in the placebo group. |
| Adverse Event(agent arm): | the most common were stomatitis, diarrhoea, fatigue, infections, rash, and peripheral oedema. The most common grade 3 or 4 drugrelated adverse events included stomatitis, diarrhoea, infections, anaemia, and fatigue. Treatment discontinuation attributed to grade 3 or 4 adverse events related to the study drug were reported in 24 patients (12%) receiving everolimus and in three (3%) receiving placebo. |
| Conclusions: | Treatment with everolimus was associated with significant improvement in progression free survival in patients with progressive lung or gastrointestinal neuroendocrine tumours. The safety findings were consistent with the known sideeffect profile of everolimus. Everolimus is the first targeted agent to show robust antitumour activity with acceptable tolerability across a broad range of neuroendocrine tumours, including those arising from the pancreas, lung, and gastrointestinal tract. |