GEP NET: algoritmo terapeutico Dottor Nicola Fazio
Basi per il trattamento Caratteristiche del paziente Caratteristiche del tumore P.S., sindrome, comorbidità Differenziazione, Ki-67 Imaging morfologico Imaging funzionale AME statement
GEP NENs: treatments NET NEC TUMORI G1-G2 CARCINOMI G3 Ki67 (NET) (70-80%) < 20% Ki67 (NEC) (20-30%) > 20% Molecular targeted agents SSA Chemotherapy (alkylating, fluoropyrimidines) PRRT Locoregional therapies Clinical trials Chemotherapy (platinumbased)
NEN: guidelines NEN guidelines
GEP NEN Localmente avanzata Metasta?ca resecabile non resecabile solo epa?ca extraepa?ca CHIRURGIA CHIRURGIA CHIRURGIA +/- trakamen? locoregionali
Different liver tumor load Strategia medica sequenziale: SSA! EVE! TMZ! clinical trials Strategia citoriduttiva per chirurgia resettiva : chemio o PRRT +/- TAE
Mai resecabile Trapiantabile
GEP NEN Localmente avanzata Metasta?ca resecabile non resecabile solo epa?ca extraepa?ca CHIRURGIA TraKamento citoriduovo TraKamento citoriduovo
Functional imaging is crucial for extra-hepatic staging IEO patient: Liver and bone mets from PNET 68 Ga-Dotatoc-PET-CT
Phase III trials with molecular targeted agents in NETs Experimental arm Control arm target tumors N of pts Author PROMID Octreotide LAR placebo SSTR-2 Functioning midgut 84 Rinke, JCO 2010 CLARINET Lanreotide autogel placebo SSTR-2 Non-functioning enteropancreatic 204 Caplin, ENETS 2014 RADIANT-2 Everolimus + Octreotide LAR Placebo + Octreotide LAR mtorc1 NET with carcinoid syndrome 429 Pavel, Lancet 2012 RADIANT-3 Everolimus +/- octreotide LAR Placebo +/- octreotide LAR mtorc1 PNET 410 Yao, NEJM 2011 RADIANT-4 Everolimus placebo mtorc1 Non-pancreatic non-functioning NET 279 Not yet presented A6181111 Sunitinib placebo VEGFR, GFR, KIT, FLT3, RET PNET 171 Raymond, NEJM 2011 SWOG Bevacizumab + Octreotide LAR Bevacizumab + IFN VEGF Non-pancreatic ongoing Not yet presented NETTER-1 177 Lu-Dotatate Octreotide LAR 60 mg SSTR-2 Midgut progressing on OCT LAR 30 mg ongoing Not yet presented
Intestinal Small bowel Rand. Phase III Functioning 1 line 42 pts 43 pts Pre-treated Materiale ad esclusivo uso interno non utilizzabile ai fini della promozione scientifica Non-functioning Lanreotide Autogel vs. placebo p=0.0002 HR=0.47 [95% CI: 0.30, 0.73] 100 90 80 70 Lanreotide Autogel 120 mg 32 events / 101 patients median, not reached 60 50 HR=0.34; 95% CI: 0.20 0.59; P=0.000072 Rinke et al.,baseline JCO Oct 2009 stability! 62% Placebo 60 events / 103 patients median, 18.0 months [95% CI: 12.1, 24.0] 40 30 22% 20 10 0 0 Baseline progression Enteropancreatic Primary endpoint: PFS (ITT population, N=204) Patients alive and with no progression (%) Pancreatic 3 6 9 12 18 Time (months) 24 27 Manca il numero dei pazienti a rischio HR=0.47; 95% CI: 0.30 0.73; P=0.0002 P-value derived from stratified log-rank test; HR derived from Cox proportional hazard model. HR, hazard ratio; ITT, intention-to-treat. Rusznieski ECC-2013
Non-functioning PNET Extra-hepatic mets! SSA beyond? SSA + EVE + CT + PRRT Online survey AIOM su SSA SSA stopped at? Incoming SSA EVE CT PRRT
Non-functioning PNET! Biologico IEO SSA EVE Clinical trial Phase IV Sunitinib Phase Ib BYL+EVE
BYL- 719: PI3Kα- inhibitor BYL BYL + EVE interna?onal phase Ib study in PNET incoming
Non-functioning ileal NET! SSA Clinical trial NETTER-1 LAN HD Phase I BYL + EVE Phase II PRRT Phase II chemo
Non-functioning non-ileal non-pancreatic NET! SSA Clinical trial Phase II PRRT LAN HD Phase I BYL + EVE Phase II chemo
Advanced progressive well-diff NETs and poorlydiff NEC Ki-67 < 55% Rand phase II TMZ + CAP conventional TMZ + CAP metronomic Stra?fica?on for SSA, SSTR, FDG, Ki- 67