Mariangela Torniai
Scuola di Specializzazione in Oncologia Medica Università Politecnica delle Marche
NOVITA’ IN TEMA DI TRATTAMENTO DELLE NEOPLASIE
NEUROENDOCRINE
NEUROENDOCRINE NEOPLASMS: WHAT’S NEW?
Basic Science
Scarpa A et al. Nature 2017
Pan-NETs have an unpredictable clinical course that varies from indolent to highly malignant
Our current understanding of the molecolar pathology of G1 and G2 PanNETs is insufficient for their clinical mangement
It is not yet possible to use molecular analysis to select patients who will benefit from specific therapies
Molecular analysis of Pan-NETs
NEUROENDOCRINE NEOPLASMS: WHAT’S NEW?
Basic Science
Scarpa A et al. Nature 2017
36 G1 57 G2 5 G3
Flow chart of the experiment
NEUROENDOCRINE NEOPLASMS: WHAT’S NEW?
Basic Science
Scarpa A et al. Nature 2017
Integrated analysis
NEUROENDOCRINE NEOPLASMS: WHAT’S NEW?
NENs treatment options
• Somatostatin analogs
• Interferon
• Others (PPI, Diazoxide)
• Telotristat
• PRRT
• Somatostatin analogs
• PRRT
• Targeted agents
• Chemotherapy
• Immunotherapy
Syndrome control
Tumor control
NEUROENDOCRINE NEOPLASMS: WHAT’S NEW?
Conventional therapy: Telotristat ethyl (TELESTAR)
Kulke MH et al. JCO 2017
6
Patients with advanced NETs may develop carcinoid syndrome, a condition associated with tumoral secretion of serotonin.
Somatostatin analogs are the standard treatment for patients with
carcinoid syndrome but they can develop recurrent symptoms during the
course of their disease.
NEUROENDOCRINE NEOPLASMS: WHAT’S NEW?
Conventional therapy: Telotristat ethyl (TELESTAR)
Kulke MH et al. JCO 2017
7
NEUROENDOCRINE NEOPLASMS: WHAT’S NEW?
Conventional therapy: Telotristat ethyl (TELESTAR)
Kulke MH et al. JCO 2017
8
NEUROENDOCRINE NEOPLASMS: WHAT’S NEW?
NENs - treatment options
• Somatostatin analogs
• Interferon
• Others (PPI, Diazoxide)
• Telotristat
• PRRT
• Somatostatin analogs
• PRRT
• Targeted agents
• Chemotherapy
• Immunotherapy
Syndrome control
Tumor control
NEUROENDOCRINE NEOPLASMS: WHAT’S NEW?
Conventional therapy: PRRT (NETTER-1)
Strosberg J et al. NEJM 2017
10
There are limited therapeutic options for patients with advanced midgut neuroendocrine tumours (20-45% of NETs) progressing on first-line
somatostatin analogue therapy.
Thousands of patients have been treated with
177Lu-Dotatate peptide
receptor radionuclide therapy (PRRT) with promising results
NEUROENDOCRINE NEOPLASMS: WHAT’S NEW?
Conventional therapy: PRRT (NETTER-1)
Strosberg J et al. NEJM 2017
11
Randomization
Stratification according to:
-
- Uptake score Octreoscan
-
- Length of treatment with octreotide
n = 116
n = 113
5 Years follow
up 4 administrations of 7.4 GBq of LUTATHERA every 8
weeks + BSC (Octreotide LAR 30 mg)
Octreotide LAR 60mg every 4 weeks
Main elegibility criteria and study design
Histologically proven midgut neuroendocrine tumors well or moderately differentiated with ki67 ≤ 20%
Advanced stage
Radiological disease progression over the course of a maximum period of 3 years during treatment with octreotide LAR 20 or 30 mg every 3 or 4 weeks
Somatostatin receptor positive disease
Including functioning and non-functioning
NEUROENDOCRINE NEOPLASMS: WHAT’S NEW?
Conventional therapy: PRRT (NETTER-1)
Strosberg J et al. NEJM 2017
12
NEUROENDOCRINE NEOPLASMS: WHAT’S NEW?
Conventional therapy: PRRT (NETTER-1)
Strosberg J et al. NEJM 2017
13
In Lu-Dotatate Group:
No evidence of renal toxicity
Mielodisplastic syndrome in
one patients
NEUROENDOCRINE NEOPLASMS: WHAT’S NEW?
Conventional therapy: PRRT (NETTER-1)
Strosberg J et al. Poster ASCO 2018
NEUROENDOCRINE NEOPLASMS: WHAT’S NEW?
NENs - treatment options
• Somatostatin analogs
• Interferon
• Others (PPI, Diazoxide)
• Telotristat
• PRRT
• Somatostatin analogs
• PRRT
• Targeted agents
• Chemotherapy
• Immunotherapy
Syndrome control
Tumor control
NEUROENDOCRINE NEOPLASMS: WHAT’S NEW?
Conventional therapy: Targeted therapy
Chan et al. ASCO GI 2017,
16
Xu J et al. ENETS 2017
PHASE III TRIALS ONGOING
NEUROENDOCRINE NEOPLASMS: WHAT’S NEW?
Conventional therapy: Targeted therapy
Iyer R et al. Poster ASCO 2018
17
NEUROENDOCRINE NEOPLASMS: WHAT’S NEW?
NENs - treatment options
• Somatostatin analogs
• Interferon
• Others (PPI, Diazoxide)
• Telotristat
• PRRT
• Somatostatin analogs
• PRRT
• Targeted agents
• Chemotherapy
• Immunotherapy
Syndrome control
Tumor control
Frenel JS et al. JCO 2017; Presented at the European Society Medical Oncology Congress, Madrid, September 8-12, 2017.
NEUROENDOCRINE NEOPLASMS: WHAT’S NEW?
Immunotherapy (KEYNOTE-028)
NEUROENDOCRINE NEOPLASMS: WHAT’S NEW?
Immunotherapy (KEYNOTE-028)
Frenel JS et al. JCO 2017; Presented at the European Society Medical Oncology Congress, Madrid, September 8-12, 2017.
NEUROENDOCRINE NEOPLASMS: WHAT’S NEW?
Immunotherapy (KEYNOTE-028)
Frenel JS et al. JCO 2017; Presented at the European Society Medical Oncology Congress, Madrid, September 8-12, 2017.
NEUROENDOCRINE NEOPLASMS: WHAT’S NEW?
Immunotherapy (KEYNOTE-028)
Frenel JS et al. JCO 2017; Presented at the European Society Medical Oncology Congress, Madrid, September 8-12, 2017.
NEUROENDOCRINE NEOPLASMS: WHAT’S NEW?
Immunotherapy (KEYNOTE-028)
Frenel JS et al. JCO 2017; Presented at the European Society Medical Oncology Congress, Madrid, September 8-12, 2017.
NEUROENDOCRINE NEOPLASMS: WHAT’S NEW?
Immunotherapy (KEYNOTE-028)
Frenel JS et al. JCO 2017; Presented at the European Society Medical Oncology Congress, Madrid, September 8-12, 2017.
NEUROENDOCRINE NEOPLASMS: WHAT’S NEW?
Immunotherapy
Puccini A. Poster ASCO 2018
GI-NENs vs Pan-NENs
LG-NENs vs HG-NENs
Vijayvergia N. Poster ASCO 2018
NEUROENDOCRINE NEOPLASMS: WHAT’S NEW?
Immunotherapy (PEMBROLIZUMAB in NECs)
Kaufman HL et l. Lancet 2016
