Faculty Opinions recommendation of Everolimus in combination with octreotide long-acting repeatable in a first-line setting for patients with neuroendocrine tumors: an ITMO group study.

Background: We previously presented data of this multicentric, phase II study showing that everolimus plus octreotide long-acting repeatable (LAR) for advanced neuroendocrine neoplasms (NENs), in the first line setting, is an active and safe treatment. We now present updated data at 5 years. Methods: Patients with advanced well-differentiated, previously untreated neuroendocrine tumors of the gastroenteropancreatic tract and of the lung received octreotide LAR 30 mg plus everolimus 10 mg/day. The primary endpoint was the objective response rate (ORR). We performed an analysis of “long responder” patients and of time to progression (TTP) and overall survival (OS) at 5 years. Results: Fifty patients were enrolled; the primary tumor site was: pancreas (14 patients), lung (11 patients), ileum (9 patients), jejunum/duodenum (2 patients), and unknown (14 patients). Seventeen (34%) of these patients have received treatment for more than 2 years. The median exposure to study drugs was 519.5 days (range 48-2,024). Currently 3 patients are still in treatment. The ORR (partial response + complete response) was 18% (95% confidence interval [CI] 7.4-28.6): complete response 1 patient (2%), partial response 8 patients (16%), stable disease 37 patients (74%). The median TTP was 33.6 months (95% CI 18.7-41.2) and the median OS was 61.0 months (95% CI 49.8-not reached). Conclusion: In this update of clinical outcome at 5-year follow-up, everolimus plus octreotide has been shown to be active in advanced NENs. The current analysis showed a further prolongation of TTP and a long exposure to the study drug without major side effects in the long term.

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Everolimus in combination with octreotide long-acting repeatable in a first-line setting for patients with neuroendocrine tumors: An ITMO group study

Cancer ◽

10.1002/cncr.28726 ◽

2014 ◽

Vol 120 (16) ◽

pp. 2457-2463 ◽

Cited By ~ 45

Author(s):

Emilio Bajetta ◽

Laura Catena ◽

Nicola Fazio ◽

Sara Pusceddu ◽

Pamela Biondani ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

First Line ◽

Long Acting ◽

Line Setting

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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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Metastatic gastroenteropancreatic neuroendocrine tumors treated with somatostatin analogues: Ten years experience in a third level hospital in Mexico City.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.514 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 514-514

Author(s):

Alberto Pimentel ◽

Abdel Karim Dip Borunda ◽

Luis Jonathan Bueno Rosario ◽

Gloria Martinez Martinez ◽

Miguel Angel Pluma ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Symptom Control ◽

Progression Free Survival ◽

Somatostatin Analogues ◽

Low Grade ◽

Common Symptom ◽

First Line ◽

Gastroenteropancreatic Neuroendocrine Tumors ◽

Long Acting

514 Background: Gastroenteropancreatic neuroendocrine tumors (GEP NET´s) are infrequent tumors, with a variety of symptoms depending of the kind of peptide they secrete as well as the affected organs. Long acting somatostatin analogues have shown an adequate rate of symptom control in functional tumors, they also have demonstrated antiproliferative effect, which is translated in a significant improvement of progression free and overall survival Methods: In this retrospective analysis of patients with metastatic GEP NET treated with long acting somatostatin analogues as first line, treated between 2005 and 2015, we evaluated clinical and pathological features, symptoms, disease control and survival adjusted with OMS classification Results: Our cohort included 95 patients with a mean age of 53 years. Primary affected sites were midgut (29.4%), followed by pNET (17.%), stomach (14.7%), and primary unknown in 14%. 20% of cases were functional tumors with diarrhea as the most common symptom in 70% and flushing in 50%. Considering the whole cohort the most prevalent symptom was abdominal pain in the 50% of cases. The OMS classification showed low grade tumors in 65% and 35% intermediate grade. Most common metastatic organ sites were; liver only 35%, liver and other 30%, peritoneum 10% and lymph nodes in 6%, non-specified sites in 19%. Somatostatine analogues used in first line were octreotide in 80% and lanreotide in 20%. Survival results demonstrated a progression free survival for the whole cohort of 84months. No differences between lanreotide and octreotide were observed. Conclusions: This study represents the first Mexican cohort of patients with GEP NET’s treated with somatostatin analogues with a long follow up.

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Phase II study of everolimus in combination with octreotide LAR as first line setting for patients with neuroendocrine tumors (I.T.M.O. study): a 5-years update

Annals of Oncology ◽

10.1093/annonc/mdv348.01 ◽

2015 ◽

Vol 26 ◽

pp. vi132

Author(s):

E. Bajetta ◽

L. Catena ◽

S. Pusceddu ◽

N. Fazio ◽

G. Blanco ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Phase Ii ◽

Phase Ii Study ◽

First Line ◽

Octreotide Lar ◽

Line Setting

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Everolimus in combination with Octreotide LAR in first line setting for patients with neuroendocrine tumors (I.T.M.O. study): A 5-years update.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.15_suppl.4092 ◽

2016 ◽

Vol 34 (15_suppl) ◽

pp. 4092-4092

Author(s):

Emilio Bajetta ◽

Laura Catena ◽

Sara Pusceddu ◽

Nicola Fazio ◽

Italo Sarno ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

First Line ◽

Octreotide Lar ◽

Line Setting

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Phase II study of everolimus in combination with octreotide LAR in first line setting for patients with neuroendocrine tumors (I.T.M.O. study): A 4-year update.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.15_suppl.e15199 ◽

2015 ◽

Vol 33 (15_suppl) ◽

pp. e15199-e15199

Author(s):

Emilio Bajetta ◽

Laura Catena ◽

Sara Pusceddu ◽

Nicola Fazio ◽

Giusi Blanco ◽

...

Keyword(s):

Neuroendocrine Tumors ◽

Phase Ii ◽

Phase Ii Study ◽

First Line ◽

Octreotide Lar ◽

Line Setting

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The Role of Wireless Capsule Endoscopy (WCE) in the Detection of Occult Primary Neuroendocrine Tumors

Journal of Gastrointestinal and Liver Diseases ◽

10.15403/jgld.2014.1121.262.wce ◽

2017 ◽

Vol 26 (2) ◽

pp. 151-156

Author(s):

Manuele Furnari ◽

Andrea Buda ◽

Gabriele Delconte ◽

Davide Citterio ◽

Theodor Voiosu ◽

...

Keyword(s):

Neuroendocrine Tumor ◽

Neuroendocrine Tumors ◽

Capsule Endoscopy ◽

Primary Tumor ◽

Diagnostic Yield ◽

Somatostatin Receptor ◽

Tertiary Care ◽

Wireless Capsule Endoscopy ◽

First Line ◽

Wireless Capsule

Background & Aims: Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms with unclear etiology that may show functioning or non-functioning features. Primary tumor localization often requires integrated imaging. The European Neuroendocrine Tumors Society (ENETS) guidelines proposed wireless-capsule endoscopy (WCE) as a possible diagnostic tool for NETs, if intestinal origin is suspected. However, its impact on therapeutic management is debated. We aimed to evaluate the yield of WCE in detecting intestinal primary tumor in patients showing liver NET metastases when first-line investigations are inconclusive.Method: Twenty-four patients with histological diagnosis of metastatic NET from liver biopsy and no evidence of primary lesions at first-line investigations were prospectively studied in an ENETS-certified tertiary care center. Wireless-capsule endoscopy was requested before explorative laparotomy and intra-operative ultrasound. The diagnostic yield of WCE was compared to the surgical exploration.Results: Sixteen subjects underwent surgery; 11/16 had positive WCE identifying 16 bulging lesions. Mini-laparotomy found 13 NETs in 11/16 patients (9 small bowel, 3 pancreas, 1 bile ducts). Agreement between WCE and laparotomy was recorded in 9 patients (Sensitivity=75%; Specificity=37.5%; PPV=55%; NPV=60%). Correspondence assessed per-lesions produced similar results (Sensitivity=70%; Specificity=25%; PPV=44%; NPV=50%). No capsule retentions were recorded.Conclusions: Wireless-capsule endoscopy is not indicated as second-line investigation for patients with gastro-entero-pancreatic NETs. In the setting of a referral center, it might provide additional information when conventional investigations are inconclusive about the primary site.Abbreviations: DBE: double balloon enteroscopy; GEP-NET: gastro-entero-pancreatic neuroendocrine tumor; GI: gastrointestinal; ENETS: European Neuroendocrine Tumor Society; NET: neuroendocrine tumor; SSRS: somatostatin receptor scintigraphy; WCE: wireless capsule endoscopy.

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Patient profiles as an aim to optimize selection in the second line setting: the role of aflibercept

Clinical & Translational Oncology ◽

10.1007/s12094-021-02568-y ◽

2021 ◽

Author(s):

B. González Astorga ◽

F. Salvà Ballabrera ◽

E. Aranda Aguilar ◽

E. Élez Fernández ◽

P. García-Alfonso ◽

...

Keyword(s):

Colorectal Cancer ◽

Therapeutic Option ◽

Scientific Evidence ◽

Treatment Options ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Effective Therapeutic Option ◽

Line Setting ◽

First Line Treatment

AbstractColorectal cancer is the second leading cause of cancer-related death worldwide. For metastatic colorectal cancer (mCRC) patients, it is recommended, as first-line treatment, chemotherapy (CT) based on doublet cytotoxic combinations of fluorouracil, leucovorin, and irinotecan (FOLFIRI) and fluorouracil, leucovorin, and oxaliplatin (FOLFOX). In addition to CT, biological (targeted agents) are indicated in the first-line treatment, unless contraindicated. In this context, most of mCRC patients are likely to progress and to change from first line to second line treatment when they develop resistance to first-line treatment options. It is in this second line setting where Aflibercept offers an alternative and effective therapeutic option, thought its specific mechanism of action for different patient’s profile: RAS mutant, RAS wild-type (wt), BRAF mutant, potentially resectable and elderly patients. In this paper, a panel of experienced oncologists specialized in the management of mCRC experts have reviewed and selected scientific evidence focused on Aflibercept as an alternative treatment.

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