Everolimus in advanced,progressive, well‐differentiated,non‐functional neuroendocrine tumors: RADIANT‐4 lung subgroup analysis |
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| Authors: | Nicola Fazio Roberto Buzzoni Gianfranco Delle Fave Margot E. Tesselaar Edward Wolin Eric Van Cutsem Paola Tomassetti Jonathan Strosberg Maurizio Voi Lida Bubuteishvili‐Pacaud Antonia Ridolfi Fabian Herbst Jiri Tomasek Simron Singh Marianne Pavel Matthew H. Kulke Juan W. Valle James C. Yao |
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| Affiliation: | 1. European Institute of Oncology, IRCCS, Milan, Italy;2. Fondazione IRCCS Foundation, The National Institute of Tumors, Milan, Italy;3. Hospital Sant'Andrea, La Sapienza University, Rome, Italy;4. Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, the Netherlands;5. Montefiore Einstein Center for Cancer Care, Bronx, NY, USA;6. University Hospitals Gasthuisberg/Leuven and KU Leuven, Leuven, Belgium;7. Department of Medical and Surgical Sciences, S. Orsola‐Malpighi Hospital, University of Bologna, Bologna, Italy;8. Moffitt Cancer Center, Tampa, FL, USA;9. Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA;10. Novartis Pharma AG, Basel, Switzerland;11. Novartis Pharma S.A.S., Rueil‐Malmaison, France;12. Faculty of Medicine, Masaryk Memorial Cancer Institute, Masaryk University, Brno, Czech Republic;13. Sunnybrook Health Sciences Centre, Toronto, ON, Canada;14. Charité University Medicine Berlin, Campus Virchow‐Klinikum, Berlin, Germany;15. Dana Farber Cancer Institute, Boston, MA, USA;16. Institute of Cancer Sciences, The Christie NHS Foundation Trust, University of Manchester, Manchester, UK;17. University of Texas MD Anderson Cancer Center, Houston, TX, USA |
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| Abstract: | In the phase III RADIANT‐4 study, everolimus improved median progression‐free survival (PFS) by 7.1 months in patients with advanced, progressive, well‐differentiated (grade 1 or grade 2), non‐functional lung or gastrointestinal neuroendocrine tumors (NETs) vs placebo (hazard ratio, 0.48; 95% confidence interval [CI], 0.35‐0.67; P < .00001). This exploratory analysis reports the outcomes of the subgroup of patients with lung NETs. In RADIANT‐4, patients were randomized (2:1) to everolimus 10 mg/d or placebo, both with best supportive care. This is a post hoc analysis of the lung subgroup with PFS, by central radiology review, as the primary endpoint; secondary endpoints included objective response rate and safety measures. Ninety of the 302 patients enrolled in the study had primary lung NET (everolimus, n = 63; placebo, n = 27). Median PFS (95% CI) by central review was 9.2 (6.8‐10.9) months in the everolimus arm vs 3.6 (1.9‐5.1) months in the placebo arm (hazard ratio, 0.50; 95% CI, 0.28‐0.88). More patients who received everolimus (58%) experienced tumor shrinkage compared with placebo (13%). Most frequently reported (≥5% incidence) grade 3‐4 drug‐related adverse events (everolimus vs. placebo) included stomatitis (11% vs. 0%), hyperglycemia (10% vs. 0%), and any infections (8% vs. 0%). In patients with advanced, progressive, well‐differentiated, non‐functional lung NET, treatment with everolimus was associated with a median PFS improvement of 5.6 months, with a safety profile similar to that of the overall RADIANT‐4 cohort. These results support the use of everolimus in patients with advanced, non‐functional lung NET. The trial is registered with ClinicalTrials.gov (no. NCT01524783). |
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| Keywords: | everolimus lung carcinoid neuroendocrine tumors progression‐free survival RADIANT‐4 |
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