Prognostic factors for progression-free survival (PFS) in CLARINET study of lanreotide depot/autogel (LAN) vs placebo (PBO) in neuroendocrine tumors (NETs).

Konference: 2015 51th ASCO Annual Meeting - účast ČR

Kategorie: Gastrointestinální nádory

Téma: Publication-only abstracts

Číslo abstraktu: e15180

Autoři: MD Edward M. Wolin; Prof. M.D. Martyn E. Caplin, FRCP; Prof. Dr. Marianne E. Pavel, M.D.; Prof. M.D. Jaroslaw B. Cwikla; Prof. M.D. Alexandria T. Phan; M.D. Markus Raderer; MUDr. Eva Sedláčková, MBA; Prof. M.D. Guillaume Cadiot, Ph.D.; MD Jaume Capdevila; M.D. Lucy R. Wall ; M.D. Guido Rindi, Ph.D.; Alison Langley; Edda Gomez-Panzani; Prof. M.D. Philippe B. Ruszniewski

Background: CLARINET showed LAN 120 mg significantly increased PFS vs PBO (hazard ratio [HR] for progressive disease [PD]/death 0.47 [95% CI: 0.30, 0.73]) in metastatic intestinal and pancreatic NETs. This was a preplanned exploratory covariate analysis to identify prognostic factors for PFS. Methods: Patients with metastatic grade 1/2 nonfunctioning intestinal/pancreatic NETs received LAN 120 mg (n=101) or PBO (n=103) for 96 wks or until PD/death (NCT00353496). Baseline covariates (as listed in table) were tested with treatment and baseline stratification factors (PD yes/no; prior therapy [PT] yes/no) in separate Cox proportional hazards (PH) models. Factors potentially significant in univariate analysis were included in stepwise multivariate (MV) analysis to obtain a final model. Treatment interaction was investigated. Results: In the final model (Table), risk of PD/death was increased in patients with: hepatic tumor load (HTL) >25%; primary tumor type of pancreas; and below-median BMI. No covariate-by-treatment interaction was significant. Adjusted for covariates, treatment with LAN vs PBO reduced the risk of PD/death by 60% (Table). Conclusions: LAN is effective across patient characteristics; risk of PD/death was lower with no PD at baseline. Exploratory analysis of other covariates identified HTL and primary tumor type as the most important prognostic factors for PFS. Effect of PT was not significant. Clinical trial information: NCT00353496

Term (reference) HR [95% CI)* P value*
LAN (PBO) 0.40 [0.25, 0.63] < 0.0001
PD (no PD) 4.57 [1.67, 12.54] 0.0032
PT (no PT) 1.29 [0.72, 2.31] 0.3914
HTL, %(0):   0.0005
>0, ≤10 0.81 [0.42, 1.59]  
>10, ≤25 1.22 [0.59, 2.52]  
>25, ≤50 2.82 [1.41, 5.63]  
>50 2.47 [1.21, 5.03]  
Primary tumor type (pancreas):   0.0289
Mid gut 0.80 [0.33, 1.94]  
Hind gut 0.53 [0.32, 0.88]  
Other / unknown 0.39 [0.17, 0.86]  
BMI >median# (≤median) 0.64 [0.41, 1.00] 0.0483

Other baseline terms (sex, age, race, US/ex-US, region, time since diagnosis, Ki67, tumor grade, CgA, prior chemotherapy, prior surgery) had no prognostic value (p>0.1) either in individual models or in presence of other terms in final model.*From final MV Cox PH model; #26.2 kg/m2;intent-to-treat population.

J Clin Oncol 33, 2015 (suppl; abstr e15180)

Datum přednesení příspěvku: 17. 5. 2015