Efficacy and safety of everolimus in advanced, progressive, nonfunctional neuroendocrine tumors (NET) of the gastrointestinal (GI) tract and unknown primary: A subgroup analysis of the phase III RADIANT-4 trial.

Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Session Type and Session Title: 
Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Abstract Number: 


Poster Board Number: 
Poster Session B Board #F17
J Clin Oncol 34, 2016 (suppl 4S; abstr 315)
Simron Singh, Carlo Carnaghi, Roberto Buzzoni, Rodney F. Pommier, Markus Raderer, Jiri Tomasek, Harald Lahner, Juan W. Valle, Maurizio Voi, Lida Bubuteishvili-Pacaud, Jeremie Lincy, Carolin Sachs, Natsuko Okita, Steven K. Libutti, Do-Youn Oh, Matthew H. Kulke, Jonathan R. Strosberg, James C. Yao, Marianne E. Pavel, Nicola Fazio, RAD001 in Advanced Neuroendocrine Tumors, Fourth Trial (RADIANT-4) Study Group; Sunnybrook Health Sciences Centre, Toronto, ON, Canada; IRCCS Istituto Clinico Humanitas, Rozzano, Italy; Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy; Oregon Health & Science University, Portland, OR; University Klinik f. Innere Medizin I, Wien, Austria; Masaryk Memorial Cancer Institute, Brno, Czech Republic; Universitaetsklinikum Essen, Zentrum f. Innere Medizin, Essen, Germany; Institute of Cancer Studies, University of Manchester, The Christie Hospital, Manchester, United Kingdom; Novartis Pharmaceuticals Corporation, East Hanover, NJ; Novartis Pharma AG, Basel, Switzerland; National Cancer Center Hospital, Chuo-ku, Tokyo, Japan; Montefiore Medical Center, Bronx, NY; Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea; Dana-Farber Cancer Institute, Boston, MA; Department of Medicine, Moffitt Cancer Center, Tampa, FL; The University of Texas MD Anderson Cancer Center, Houston, TX; Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany; Istituto Europeo di Oncologia, IRCCS, Milan, Italy

Abstract Disclosures


Background: In the groundbreaking, phase 3 RCT RADIANT-4 study, everolimus (EVE) significantly prolonged median progression-free survival (PFS) by 7.1 mo in patients (pts) with advanced, progressive, nonfunctional NET of GI or lung vs placebo (PBO); HR, 0.48 (95%CI, 0.35-0.67), P<0.00001 [Yao JC et al, ECC-ESMO, 2015]. Methods: InRADIANT-4, pts with advanced, progressive, well-differentiated (G1/G2), nonfunctional GI or lung NET were randomized (2:1) to EVE (10 mg/d) or PBO. In this analysis, pts with NET of GI tract (stomach, colon, rectum, appendix, caecum, ileum, duodenum, jejunum, or small intestine) and unknown primary were included. Results: Of 302 pts, 175 had GI NET (EVE [n=118], PBO [n=57]); 36 had NET of unknown primary (EVE [23], PBO [13]). In GI NET pts, median age was 63 y; females: 55%; G1/G2: 75%/25%; WHO PS: 0, 78% or 1, 22%; Caucasian: 73%. Similar baseline characteristics were observed in pts with NET of unknown primary. Ileum (41%), rectum (23%) and jejunum (13%) were the most common locations in GI subgroup. The table below lists prior treatments. In pts with GI NET, median PFS (95% CI) by central review (EVE vs PBO) was 13.1 (9.2-17.3) mo vs 5.4 (3.6-9.3) mo with an estimated 44% risk-reduction in favor of EVE (HR, 0.56; 95% CI, 0.37-0.84). In pts with NET of unknown primary, median PFS (95% CI) by central review (EVE vs PBO) was 13.6 (4.1-not evaluable) mo vs 7.5 (1.9-18.5) mo (HR, 0.60; 95% CI, 0.24-1.51). The most frequent G3/4 adverse events irrespective of drug-relationship reported in ≥5% pts in GI subgroup were diarrhea, hypertension, stomatitis, abdominal pain, fatigue, and acute renal failure. Conclusions: The present subgroup analysis of RADIANT-4 study demonstrated improvement in PFS with EVE for pts with GI NET, and suggests efficacy in NET of unknown primary, with an estimated 40% to 44% risk-reduction in favor of EVE vs PBO. Safety profile for EVE is consistent with that previously reported. Clinical trial information: NCT01524783

Prior therapies.

Prior TherapyGI (N=175)
Unknown Primary (N=36)
EVE (n=118)PBO (n=57)EVE (n=23)PBO (n=13)
SSA (tumor control)59%63%52%54%