Everolimus plus octreotide LAR versus placebo plus octreotide LAR in patients (pts) with advanced neuroendocrine tumors: Multivariate analysis of progression-free survival from the RADIANT-2 trial.

Abstract

e21084 Background: In the phase III RADIANT-2 trial, everolimus, an oral inhibitor of mTOR, plus octreotide (E+O) demonstrated a clinically meaningful increase in median progression-free survival (PFS) compared with placebo + octreotide LAR (P+O) in pts with advanced low- or intermediate-grade NET and a history of secretory symptoms associated with carcinoid syndrome (ESMO 2010 Abstract #LBA8). In order to determine the factors that significantly influence PFS, a multivariate analysis was performed. Methods: Pts with advanced NET were randomized to oral everolimus 10 mg/d + octreotide LAR 30 mg IM q 28 days (n=216) or P+O (n=213). The primary endpoint was PFS per adjudicated central review (RECIST v1.0). Multivariate analysis using a Cox-proportional hazards model was performed. Significant factors (p<0.05) were determined after a stepwise elimination of the nonsignificant factors from the model. Results: Multivariate analysis indicated that significant prognostic factors for PFS were treatment (everolimus vs placebo) (p=0.001), WHO performance status (p=0.007), lung as primary site (p=0.044), baseline CgA (p<0.001), and bone involvement (p=0.022) (Table). Conclusions: Multivariate analysis of the RADIANT-2 trial has allowed, for the first time, evaluation of the prognostic risk factors associated with PFS in a large phase III, placebo-controlled trial in pts with advanced NET. A better understanding of these risk factors can help clinicians in the treatment of their pts. Multivariate analysis of PFS. N Median PFS (95% CI) Hazard ratio (95% CI) P Treatment 0.62 (0.47, 0.82) 0.001 E+O 216 16.43 (13.67, 21.19) P+O 213 11.3 (8.44, 14.59) WHO performance status 0.69 (0.52, 0.90) 0.007 0 257 16.62 (13.63, 20.27) ≥1 170 11.10 (8.31, 14.23) Lung as primary site 1.55 (1.01, 2.36) 0.044 Yes 44 10.61 (5.55, 14.23) No 385 14.23 (11.96, 17.68) Baseline CgA 2.11 (1.53, 2.91) <0.001 Elevated 282 11.33 (9.66, 13.80) Nonelevated 138 26.84 (17.68, NA) Bone involvement 1.52 (1.06, 2.18) 0.022 Yes 59 8.31 (5.32, 13.83) No 367 15.38 (13.04, 19.19)