Evaluating bevacizumab in combination with FOLFIRI after the failure of platinum-etoposide regimen in patients with advanced poorly differentiated neuroendocrine carcinoma: The PRODIGE 41–BEVANEC randomized phase II study

Walter, Thomas; Malka, David; Hentic, Olivia; Lombard‐Bohas, Catherine; Malicot, Karine Le; Smith, Denis; Ferru, Aurélie; Assenat, Éric; Cadiot, Guillaume; Lièvre, Astrid; Kurtz, Jean‐Emmanuel; Dahan, Laétitia; Dubreuil, Olivier; Hautefeuille, Vincent; Lepère, Céline; Gangloff, Alice; El-Hajbi, Farid; Roquin, Guillaume; Bouarioua, Nadia; Granger, Victoire; Scoazec, Jean‐Yves; Lepage, Côme

doi:10.1016/j.dld.2017.11.020

Cited by 19 publications

(14 citation statements)

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“…In addition, the data from the present study, although nonstatistically significant and mostly derived in the second-line setting, indicates that a fluoropyrimidine/irinotecan combination could be more effective in non-SC EP-NECs. This is being explored in two randomised phase II studies: BEVANEC is evaluating the FOLFIRI regimen +/− bevacizumab as a second-line treatment after the failure of platinumetoposide regimen in 124 patients with advanced GEP-NEC [30]; the NET-02 study is investigating a 5-fluorouracil/folinic acid/liposomal irinotecan combination or docetaxel as a single agent in 102 patients with available EP-NEC tissue who have failed platinumbased chemotherapy (at https://clinicaltrials.gov/ct2/show/NCT03837977, accessed on 30 June 2021). The NET-02 trial will provide insights on the activity of these two alternative regimens in EP-NECs, and future post-hoc analyses may unveil associations with the morphological subtype [31].…”

Section: Discussionmentioning

confidence: 99%

Is the Morphological Subtype of Extra-Pulmonary Neuroendocrine Carcinoma Clinically Relevant?

Frizziero

Durand

Taboada

et al. 2021

Cancers

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Extra-pulmonary neuroendocrine carcinomas (EP-NECs) are lethal cancers with limited treatment options. Identification of contributing factors to the observed heterogeneity of clinical outcomes within the EP-NEC family is warranted, to enable identification of effective treatments. A multicentre retrospective study investigated potential differences in “real-world” treatment/survival outcomes between small-cell (SC) versus (vs.) non-SC EP-NECs. One-hundred and seventy patients were included: 77 (45.3%) had SC EP-NECs and 93 (54.7%) had non-SC EP-NECs. Compared to the SC subgroup, the non-SC subgroup had the following features: (1) a lower mean Ki-67 index (69.3% vs. 78.7%; p = 0.002); (2) a lower proportion of cases with a Ki-67 index of ≥55% (73.9% vs. 88.7%; p = 0.025); (3) reduced sensitivity to first-line platinum/etoposide (objective response rate: 31.6% vs. 55.1%, p = 0.015; and disease control rate; 59.7% vs. 79.6%, p = 0.027); (4) worse progression-free survival (PFS) (adjusted-HR = 1.615, p = 0.016) and overall survival (OS) (adjusted-HR = 1.640, p = 0.015) in the advanced setting. Within the advanced EP-NEC cohort, subgroups according to morphological subtype and Ki-67 index (<55% vs. ≥55%) had significantly different PFS (adjusted-p = 0.021) and OS (adjusted-p = 0.051), with the non-SC subgroup with a Ki-67 index of <55% and non-SC subgroup with a Ki-67 index of ≥55% showing the best and worst outcomes, respectively. To conclude, the morphological subtype of EP-NEC provides complementary information to the Ki-67 index and may aid identification of patients who could benefit from alternative first-line treatment strategies to platinum/etoposide.

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Section: Discussionmentioning

confidence: 99%

Is the Morphological Subtype of Extra-Pulmonary Neuroendocrine Carcinoma Clinically Relevant?

Frizziero

Durand

Taboada

et al. 2021

Cancers

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“…These poor results, however, highlight the need to find more effective new treatments against NEC. Some studies are ongoing, testing targeted therapies such as bevacizumab in association with FOLFIRI ( 17 ) or everolimus (NCT02113800), or immunotherapy (NCT03591731 and NCT03866382).…”

Section: Discussionmentioning

confidence: 99%

Post first-line dacarbazine or temozolomide in neuroendocrine carcinoma

Couronne

Girot

Hadoux

et al. 2020

Endocrine Connections

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Objective First-line chemotherapy in metastatic neuroendocrine carcinomas (NECs) is based on etoposide and platinum. However, there is no standard concerning second-line treatment. The objective of this study was to evaluate efficacy and tolerance of dacarbazine or temozolomide in metastatic digestive NEC as post first-line treatment. Material and methods This study included patients with a metastatic NEC of digestive or unknown primary site. All patients received platinum-etoposide as first-line chemotherapy. Primary endpoint was progression-free survival (PFS). Secondary endpoints were clinical/morphological responses, toxicity, and overall survival (OS). Results Twenty-seven patients were included: 17 received dacarbazine and 10 temozolomide as post-first line treatments. Median PFS was 3.0 (95%CI (2.2;3.7)) months. There was no significant difference between dacarbazine and temozolomide on PFS. Clinical and morphological responses were found in 12 and 9 patients, respectively. Median OS was 7.2 (95%CI (2.2;12.2)) months. The toxicity profile was that expected with such treatments. Conclusion LV5FU2-dacarbazine or temozolomide-capecitabine chemotherapies allow a temporary clinical response for almost half of patients and/or a morphological response for a third of patients.

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“…Currently, available therapies include chemotherapy, targeted therapy, and peptide receptor radionuclide therapy (PRRT). Poorly-differentiated neuroendocrine carcinoma (NEC) is treated with cisplatin (or carboplatin) plus etoposide in rst-line palliative chemotherapy [20]. In a study of systemic chemotherapy on GEP-NEC at 23 hospitals in Japan, irinotecan plus cisplatin (IP) and etoposide plus cisplatin (EP) were the most used regimens.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological Features and Prognosis of Gastric Neuroendocrine Neoplasms

Wang

Wen

Tian

et al. 2020

Preprint

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Abstract Purpose: We performed a retrospective study to investigate the relationship between clinicopathological features and prognosis of G-NEN.Methods: Clinicopathological features and follow-up data of 67 patients with G-NEN treated at Shandong Provincial Hospital affiliated of Shandong University were analyzed retrospectively. Results: This whole cohort included 53 males and 14 females, with a mean age of 59.37±9.80 years. The clinical symptoms and the primary tumor site were not specific. Neuroendocrine tumor, neuroendocrine carcinoma, and mixed neuroendocrine–non‐neuroendocrine neoplasm accounted for 14.93%, 59.70%, and 25.37%, respectively. TNM stages Ⅰ-Ⅳ: 6, 6, 49, 4, respectively. All patients underwent surgically treated. Forty-five patients underwent laparoscopic surgery, and twenty-two patients received an open approach. The median survival time was 36 months in all patients. The overall survival rate for the entire cohort was 68.1 %, 44.7 %, and 34.5% at 1, 3, and 5 years, respectively. Logistic regression analysis revealed that the invasive depth of tumors was predictors for metastasis. The univariate analysis confirmed that smoking, T stage, distant metastasis, and surgical method were related to survival. COX regression analysis showed that the T stage (HR=4.817, 95%CI: 1.021-22.729, P=0.047) was an independent risk factor for evaluating the prognosis of patients with G-NEN.Conclusions: G-NEN is a kind of rare tumors that can occur at any part of the stomach. The clinical features are not specific. The tumor invasive depth related to tumor metastasis. The prognosis is associated with smoking, T stage, distant metastasis, and surgical method. Of them, T stage is an independent prognostic factor for G-NEN patients. But larger studies are needed in the future.

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Evaluating bevacizumab in combination with FOLFIRI after the failure of platinum-etoposide regimen in patients with advanced poorly differentiated neuroendocrine carcinoma: The PRODIGE 41–BEVANEC randomized phase II study

Cited by 19 publications

References 21 publications

Is the Morphological Subtype of Extra-Pulmonary Neuroendocrine Carcinoma Clinically Relevant?

Is the Morphological Subtype of Extra-Pulmonary Neuroendocrine Carcinoma Clinically Relevant?

Post first-line dacarbazine or temozolomide in neuroendocrine carcinoma

Clinicopathological Features and Prognosis of Gastric Neuroendocrine Neoplasms

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