Everolimus e octreotide LAR nel carcinoide differenziato metastatico

Introduction: Somatostatin analogues (SSA) prolong progression-free survival (PFS) in patients with well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). However, the eligibility criteria in randomized clinical trials (RCTs) have been restricted, which contrasts with the vast heterogeneity found in NETs. Methods: We identified patients with well-differentiated (Ki67% ≤20%), metastatic GEP-NETs treated in first-line with SSA monotherapy from the Spanish R-GETNE registry. The therapeutic effect was evaluated using a Bayesian Cox model. The objective was to compare survival-based outcomes from real world clinical practice versus RCTs. Results: The dataset contained 535 patients with a median age of 62 years (range: 26-89). The median Ki67% was 4 (range: 0-20). The most common primary tumor sites were: midgut, 46%; pancreas, 34%; unknown primary, 10%; and colorectal, 10%. Half of the patients received octreotide LAR (n=266) and half, lanreotide autogel (n=269). The median PFS was 28.0 months (95% CI, 22.1-32.0) for octreotide vs 30.1 months (95% CI, 23.1-38.0) for lanreotide. The overall hazard ratio for lanreotide vs octreotide was 0.90 (95% credible interval, 0.71-1.12). The probability of effect sizes >30% with lanreotide vs octreotide was 2% and 6% for midgut and foregut NENs, respectively. Conclusion: Our study evaluated the external validity of RCTs examining SSAs in the real world, as well as the main effect-modifying factors (progression status, symptoms, tumor site, specific metastases, and analytical data).. Our results indicate that both octreotide LAR and lanreotide autogel had a similar effect on PFS. Consequently, both represent valid alternatives in patients with well-differentiated, metastatic GEP-NENs.

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Comparison of primary octreotide-lar and surgical treatment in newly diagnosed patients with acromegaly

Clinical Endocrinology ◽

10.1111/j.1365-2265.2011.04106.x ◽

2011 ◽

Vol 75 (5) ◽

pp. 678-684 ◽

Cited By ~ 17

Author(s):

Z. Karaca ◽

F. Tanriverdi ◽

G. Elbuken ◽

I. Cakir ◽

H. Donmez ◽

...

Keyword(s):

Surgical Treatment ◽

Newly Diagnosed ◽

Octreotide Lar

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Octreotide LAR vs. surgery in newly diagnosed patients with acromegaly: a randomized, open-label, multicentre study

Yearbook of Endocrinology ◽

10.1016/s0084-3741(09)79387-4 ◽

2009 ◽

Vol 2009 ◽

pp. 269-270

Author(s):

W.H. Ludlam

Keyword(s):

Multicentre Study ◽

Newly Diagnosed ◽

Open Label ◽

Octreotide Lar

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A phase II/III randomized double-blind study of octreotide acetate LAR with axitinib versus octreotide acetate LAR with placebo in patients with advanced G1-G2 NETs of non-pancreatic origin (AXINET trial-GETNE-1107).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.360 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 360-360

Author(s):

Rocio Garcia-Carbonero ◽

Marta Benavent ◽

Paula Jiménez Fonseca ◽

Daniel Castellano ◽

Teresa Alonso ◽

...

Keyword(s):

Disease Progression ◽

Phase Ii ◽

Primary Tumor ◽

Phase Iii ◽

Study Entry ◽

Tumor Site ◽

Double Blind ◽

Primary Tumor Site ◽

Octreotide Lar ◽

Octreotide Acetate

360 Background: Angiogenesis plays an important role in NET development and progression. Axitinib is a potent and selective VEGFR-1,2,3 inhibitor, with proven activity against several vascular-dependent solid tumors. The aim of this randomized, double-blind phase II/III study was to assess the efficacy of axitinib in patients with advanced G1-2 extra-pancreatic NETs. Methods: Eligible pts were randomized (1:1) to receive octreotide LAR (30 mg IM q4w) with axitinib (5 mg BID) or placebo BID until disease progression or unacceptable toxicity. Pteswere stratified by time from diagnosis to study entry ( > or < 12m), primary tumor site (GI tract vs non-GI) and Ki-67 index (< 5% vs > 5%). Prior therapy with SSA, IFN and up to 2 lines of systemic treatment was allowed, but not prior VEGF- or VEGFR-targeted drugs. Clinical and/or radiological disease progression within 12 months prior to study entry was required. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), time to progression, overall response rate (ORR), duration of response, biochemical response and safety. Results: 256 pts were randomized (106 in the Phase II part, and 150 additional pts in the Phase III part), 126 to axitinib and 130 to placebo. The main characteristics of the study population were: median age 61 years (range: 21-85), 52% male, PS 0-1 (64-35%), G1-2 (29%-71%), primary tumor site GI (40%)-Lung (17%)-Other (32%). Prior therapies included: SSA (46%), everolimus (13%), chemotherapy (13%), TACE (5%) and PRRT (2%). ORR was significantly higher in axitinib- vs placebo-treated patients (17.5% vs 3.8%, p = 0.0004). PFS per investigator assessment also favored axitinib vs placebo-treated patients, although the difference did not reach statistical significance (median PFS 17.2 vs 12.3 months, respectively, HR 0.816, p = 0.169). Grade 3-4 treatment-related AEs occurred more frequently in the axitinib vs placebo arm (52% vs 13.8%), and included hypertension (21% vs 6 %), cardiac disorders (3.2% vs 0.7%), diarrhoea (13% vs 1.5 %), asthenia (9% vs 3%) and nausea&vomiting (2% vs 0.7%). There were 3 treatment-related deaths, 1 in the axitinib arm (cardiac failure) and 2 in the placebo arm (myocardial infarction and hepatorenal syndrome). Conclusions: Although the study failed to demonstrate a significant PFS benefit per investigator assessment, axitinib in combination with octreotide LAR demonstrated activity and had a tolerable safety profile in patients with advanced G1-2 extra-pancreatic NETs. Data base cleaning and central blinded radiological PFS assessment are currently ongoing. Clinical trial information: NCT01744249.

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Somatostatin receptors subtypes 2 and 5, dopamine receptor type 2 expression and gsp status as predictors of octreotide LAR® responsiveness in acromegaly

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302008000800014 ◽

2008 ◽

Vol 52 (8) ◽

pp. 1288-1295 ◽

Cited By ~ 8

Author(s):

Leonardo Vieira Neto ◽

Giselle Fernandes Taboada ◽

Mônica Roberto Gadelha

Keyword(s):

Growth Hormone ◽

Quantitative Analysis ◽

Dopamine Receptor ◽

Molecular Analysis ◽

Somatostatin Receptor ◽

Somatostatin Receptors ◽

Laboratory Data ◽

Octreotide Lar ◽

Acute Test ◽

Igf I

We present two acromegalic patients in which clinical and molecular data are discussed in regard to their ability to predict long term octreotide LAR® therapy response. Case reports: Patient 1: female, 36 years old at diagnosis. Basal GH and IGF-I at diagnosis were 133 ng/mL and 181% above the upper limit of reference values (ULRV), respectively. Growth hormone during acute test with subcutaneous octreotide decreased from 133 to 13 ng/mL. Patient started on primary octreotide LAR® therapy (20mg q28 days) and achieved biochemical parameters of disease control after 6 months. Molecular analysis of tumor fragments: gsp +; quantitative analysis of SSTR (somatostatin receptor) and DR (dopamine receptor) mRNA - SSTR2 23954; SSTR5 2407; DR2 total 17016 copies. Patient 2: male, 38 years old at diagnosis. Basal GH and IGF-I at diagnosis were 120 ng/mL and 114% ULRV, respectively. Patient underwent non-curative trans-sphenoidal surgery. Post-operative GH and IGF-I were 112 ng/mL and 137% ULRV, respectively. Growth hormone during acute test with subcutaneous octreotide decreased from 112 to 7 ng/mL. Octreotide LAR® therapy (20 mg q28 days) was then initiated. After 6 months of treatment, patient did not attain biochemical control of disease and displayed increased tumor volume. Molecular analysis of tumor fragments: gsp not done; quantitative analysis of SSTR and DR mRNA - SSTR2 416; SSTR5 3767; DR2 total 3439 copies. In conclusion, these two cases illustrate how laboratory data can be conflicting as predictors of octreotide LAR® responsiveness and how molecular analysis of tumor fragments can help explain different behaviors in clinically similar patients.

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Cost reduction from resolution/improvement of carcinoid syndrome symptoms following treatment with above-standard dose of octreotide LAR

Journal of Medical Economics ◽

10.1080/13696998.2017.1337019 ◽

2017 ◽

Vol 20 (9) ◽

pp. 945-951 ◽

Cited By ~ 3

Author(s):

Lynn Huynh ◽

Todor Totev ◽

Francis Vekeman ◽

Maureen P. Neary ◽

Mei S. Duh ◽

...

Keyword(s):

Cost Reduction ◽

Carcinoid Syndrome ◽

Standard Dose ◽

Octreotide Lar ◽

Resolution Improvement

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177Lu-DOTATATE Plus Radiosensitizing Capecitabine Versus Octreotide Long-Acting Release as First-Line Systemic Therapy in Advanced Grade 1 or 2 Gastroenteropancreatic Neuroendocrine Tumors: A Single-Institution Experience

JCO Global Oncology ◽

10.1200/go.21.00103 ◽

2021 ◽

pp. 1167-1175

Author(s):

Swayamjeet Satapathy ◽

Bhagwant R. Mittal ◽

Ashwani Sood ◽

Apurva Sood ◽

Rakesh Kapoor ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Systemic Therapy ◽

Objective Response ◽

Progression Free Survival ◽

First Line ◽

Gastroenteropancreatic Neuroendocrine Tumors ◽

Free Survival ◽

Octreotide Lar ◽

Treatment Naïve ◽

Long Acting

PURPOSE To compare the efficacy and safety of 177Lu-DOTATATE plus radiosensitizing capecitabine and octreotide long-acting release (LAR) as first-line systemic therapy in advanced well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). MATERIALS AND METHODS Data of consecutive patients of advanced inoperable or metastatic grade 1 or 2 GEP-NETs treated with first-line 177Lu-DOTATATE plus radiosensitizing capecitabine or octreotide LAR from September 2012 to December 2019 were collected and analyzed for response, toxicity, and survival outcomes. RESULTS Seventy-six patients (median age: 53 years; range 14-81 years) with treatment-naïve advanced grade 1 or 2 GEP-NETs were included. Thirty-six patients received a median cumulative dose of 27.3 GBq of 177Lu-DOTATATE intravenously at 8-12 weeks' intervals along with 1,250 mg/m2 oral capecitabine on days 0-14 of each cycle of 177Lu-DOTATATE, whereas 40 patients were administered 30 mg octreotide LAR intramuscularly every 4 weeks. Using response evaluation criteria in solid tumor 1.1, the objective response rate was 38% in the 177Lu-DOTATATE arm compared with 15% in the octreotide LAR arm ( P = .025), whereas the disease control rates were 88% and 67% in 177Lu-DOTATATE and octreotide LAR arms, respectively ( P = .035). The median durations of progression-free survival in the 177Lu-DOTATATE and octreotide LAR arms were 54 months and 16 months, respectively ( P = .017), whereas the median overall survival was not reached and not significantly different across both the arms. Of the treatment-related adverse events, no major difference was observed in the occurrence of grade 3 or 4 toxicities between the two treatment arms. CONCLUSION First-line systemic 177Lu-DOTATATE plus radiosensitizing capecitabine achieved better radiologic response and longer progression-free survival compared with octreotide LAR in patients with advanced grade 1 or 2 GEP-NETs. Future randomized controlled trials are, however, required to determine the best treatment sequence for the treatment-naïve patients with advanced GEP-NETs.

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