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Nivolumab plus platinum-doublet chemotherapy in treatment-naive patients with advanced grade 3 Neuroendocrine Neoplasms of gastroenteropancreatic or unknown origin: The multicenter phase 2 NICE-NEC trial (GETNE-T1913).

ABSTRACT: The prognosis of patients with advanced high-grade (G3) digestive neuroendocrine neoplasms (NENs) is rather poor. The addition of immune checkpoint inhibition to platinum-based chemotherapy may improve survival. NICE-NEC (NCT03980925) is a single-arm, phase II trial that recruited chemotherapy-naive, unresectable advanced or metastatic G3 NENs of gastroenteropancreatic (GEP) or unknown origin. Patients received nivolumab 360 mg intravenously (iv) on day 1, carboplatin AUC 5 iv on day 1, and etoposide 100 mg/m²/d iv on days 1-3, every 3 weeks for up to six cycles, followed by nivolumab 480 mg every 4 weeks for up to 24 months, disease progression, death or unacceptable toxicity. The primary endpoint was the 12-month overall survival (OS) rate (H₀ 50%, H₁ 72%, β 80%, α 5%). Secondary endpoints were objective response rate (ORR), duration of response (DoR), progression-free survival (PFS), and safety. From 2019 to 2021, 37 patients were enrolled. The most common primary sites were the pancreas (37.8%), stomach (16.2%) and colon (10.8%). Twenty-five patients (67.6%) were poorly differentiated carcinomas (NECs) and/or had a Ki67 index >55%. The ORR was 56.8%. Median PFS was 5.7 months (95%CI: 5.1-9) and median OS 13.9 months (95%CI: 8.3-Not reached), with a 12-month OS rate of 54.1% (95%CI: 40.2-72.8) that did not meet the primary endpoint. However, 37.6% of patients were long-term survivors (>2 years). The safety profile was consistent with previous reports. There was one treatment-related death. Nivolumab plus platinum-based chemotherapy was associated with prolonged survival in over one-third of chemonaïve patients with G3 GEP-NENs, with a manageable safety profile.

SUBMITTER: Riesco-Martinez MC

PROVIDER: S-EPMC11310219 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Nivolumab plus platinum-doublet chemotherapy in treatment-naive patients with advanced grade 3 Neuroendocrine Neoplasms of gastroenteropancreatic or unknown origin: The multicenter phase 2 NICE-NEC trial (GETNE-T1913).

Riesco-Martinez Maria Carmen MC Capdevila Jaume J Alonso Vicente V Jimenez-Fonseca Paula P Teule Alex A Grande Enrique E Sevilla Isabel I Benavent Marta M Alonso-Gordoa Teresa T Custodio Ana A Anton-Pascual Beatriz B Hernando Jorge J Polo Eduardo E Castillo-Trujillo Oscar Alfredo OA Lamas-Paz Arantza A Teijo Ana A Rodriguez-Gil Yolanda Y Soldevilla Beatriz B Garcia-Carbonero Rocio R

Nature communications 20240808 1

The prognosis of patients with advanced high-grade (G3) digestive neuroendocrine neoplasms (NENs) is rather poor. The addition of immune checkpoint inhibition to platinum-based chemotherapy may improve survival. NICE-NEC (NCT03980925) is a single-arm, phase II trial that recruited chemotherapy-naive, unresectable advanced or metastatic G3 NENs of gastroenteropancreatic (GEP) or unknown origin. Patients received nivolumab 360 mg intravenously (iv) on day 1, carboplatin AUC 5 iv on day 1, and etop ...[more]

PMID: 39117670

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Project description:Our understanding about the epidemiological aspects, pathogenesis, molecular diagnosis, and targeted therapies of neuroendocrine neoplasms (NENs) have drastically advanced in the past decade. Gastroenteropancreatic (GEP) NENs originate from the enteroendocrine cells of the embryonic gut which share common endocrine and neural differentiation factors. Most NENs are well-differentiated, and slow growing. Specific neuroendocrine biomarkers that are used in the diagnosis of functional NENs include insulin, glucagon, vasoactive intestinal polypeptide, gastrin, somatostatin, adrenocorticotropin, growth hormone releasing hormone, parathyroid hormone-related peptide, serotonin, histamine, and 5-hydroxy indole acetic acid (5-HIAA). Biomarkers such as pancreatic polypeptide, human chorionic gonadotrophin subunits, neurotensin, ghrelin, and calcitonin are used in the diagnosis of non-functional NENs. 5-HIAA levels correlate with tumour burden, prognosis and development of carcinoid heart disease and mesenteric fibrosis, however several diseases, medications and edible products can falsely elevate the 5-HIAA levels. Organ-specific transcription factors are useful in the differential diagnosis of metastasis from an unknown primary of well-differentiated NENs. Emerging novel biomarkers include circulating tumour cells, circulating tumour DNA, circulating micro-RNAs, and neuroendocrine neoplasms test (NETest) (simultaneous measurement of 51 neuroendocrine-specific marker genes in the peripheral blood). NETest has high sensitivity (85%-98%) and specificity (93%-97%) for the detection of gastrointestinal NENs, and is useful for monitoring treatment response, recurrence, and prognosis. In terms of management, surgery, radiofrequency ablation, symptom control with medications, chemotherapy and molecular targeted therapies are all considered as options. Surgery is the mainstay of treatment, but depends on factors including age of the individual, location, stage, grade, functional status, and the heredity of the tumour (sporadic vs inherited). Medical management is helpful to alleviate the symptoms, manage inoperable lesions, suppress postoperative tumour growth, and manage recurrences. Several molecular-targeted therapies are considered second line to somatostatin analogues. This review is a clinical update on the pathophysiological aspects, diagnostic algorithm, and management of GEP NENs.

Project description:BackgroundThe epidemiologic trends and survival related to early-onset gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) have not been well explored.MethodsTrends in the incidence and incidence-based mortality of early-onset GEP-NENs between 1975 and 2018 were obtained from the Surveillance, Epidemiology, and End Results database, and were stratified by age, sex, race, tumor site, stage, and grade. Associated population data were used to determine overall survival (OS) and independent prognostic factors for patients with early-onset GEP-NENs.ResultsA total of 17299 patients diagnosed with early-onset GEP-NENs were included in this study. Results revealed an increase in the incidence (5.95% per year, 95% confidence interval (CI), 5.75-6.14%) and incidence-based mortality (4.24% per year, 95% CI, 3.92-4.56%) for early-onset GEP-NENs from 1975 to 2018, with higher rates of increase than those of later-onset GEP-NENs (incidence: 4.45% per year, 95% CI, 4.38-4.53; incidence-based mortality: 4.13% per year, 95% CI, 3.89-4.37; respectively). Increases in incidence were observed across all age, races, tumor sites, grades, and stages, except for patients with unknown stage. Compared to those with later-onset GEP-NENs, a higher proportion of female gender (54.5% vs. 49.0%, p <0.001), well-differentiated tumor (31.1% vs. 28.0%, p <0.05), and localized disease (55.2% vs. 46.7%, p <0.05) were observed in the cohort of patients with early-onset GEP-NENs. Moreover, early-onset GEP-NENs exhibited a superior overall survival in comparison to later-onset GEP-NENs, irrespective of tumor site, grade, or stage (p <0.0001). Multivariable survival analysis identified that race, marital status, stage, grade, chemotherapy, and primary site were significantly correlated with OS in individuals with early-onset GEP-NENs.ConclusionsThe incidence and incidence-based mortality rates of early-onset GEP-NENs have steadily increased over time, with higher rates of increase than those of later-onset GEP-NENs. The clinical characteristics and survival were different between early-onset and later-onset GEP-NENs groups. Race, marital status, stage, grade, chemotherapy, and primary site were independent prognostic factors for early-onset GEP-NENs. Further investigations are warranted to better understand the characteristics of this disease subgroup.

Dataset Information

Nivolumab plus platinum-doublet chemotherapy in treatment-naive patients with advanced grade 3 Neuroendocrine Neoplasms of gastroenteropancreatic or unknown origin: The multicenter phase 2 NICE-NEC trial (GETNE-T1913).

Publications

Nivolumab plus platinum-doublet chemotherapy in treatment-naive patients with advanced grade 3 Neuroendocrine Neoplasms of gastroenteropancreatic or unknown origin: The multicenter phase 2 NICE-NEC trial (GETNE-T1913).

Similar Datasets

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