Efficacy of everolimus plus octreotide LAR in patients with advanced neuroendocrine tumor and carcinoid syndrome: final overall survival from the randomized, placebo-controlled phase 3 RADIANT-2 study

Pavel, Marianne; Baudin, Éric; Öberg, Kjell; Hainsworth, John D.; Voi, Maurizio; Rouyrre, Nicolas; Peeters, Marc; Gross, David J.; Yao, James C.

doi:10.1093/annonc/mdx193

Cited by 97 publications

(64 citation statements)

References 9 publications

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“…Nevertheless, dedicated analyses from the most recent prospective placebo-controlled trials , Pavel et al 2017b) demonstrated no CgA role for predicting the impact of a medical treatment on survival. However, it is important to remark that CgA, per definition, can be used as a marker only in NENs showing abnormal serum level.…”

Section: Resultsmentioning

confidence: 99%

“…This thesis was subsequently confirmed by RADIANT-2 and -3, which were randomized, placebocontrolled trials of everolimus in advanced NENs with carcinoid syndrome under SSA treatment and advanced pancreatic NENs, respectively (Pavel et al 2011, Yao et al 2011b. Indeed, recent post hoc analyses of both studies specifically assessed whether baseline CgA levels were only prognostic or had actual capability of predicting treatment effect on OS , Pavel et al 2017b. This was done by adjusting OS of the 2 study arms for pre-treatment CgA levels, which were imbalanced.…”

Section: Baseline Cga As Predictive Marker Of Treatment Efficacymentioning

confidence: 88%

“…Authors identified basal CgA levels less than 200 ng/mL as a positive prognostic factor, and this result was confirmed after a multivariate analysis. To date, prospective evidence about this issue has been provided by the RADIANT-1, -2 and -3 trials, where dedicated analyses were performed in order to assess a prognostic value of circulating CgA in the whole cohort of advanced NENs, independently of the prediction of treatment efficacy (Yao et al 2008b, 2010, Pavel et al 2017b. These studies considered patients showing circulating levels higher than 2-fold the upper normal limit as CgA secretors, while subjects with marker levels equal or below this cut-off were classified as having non-elevated CgA.…”

Section: Circulating Cga As a Prognostic Marker In Nenmentioning

confidence: 99%

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Chromogranin A as circulating marker for diagnosis and management of neuroendocrine neoplasms: more flaws than fame

Marotta

Zatelli

Sciammarella³

et al. 2018

Endocrine-Related Cancer

125

104

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Owing to the heterogeneity of neuroendocrine neoplasms (NENs), the availability of reliable circulating markers is critical for improving diagnostics, prognostic stratification, follow-up and definition of treatment strategy. This review is focused on chromogranin A (CgA), a hydrophilic glycoprotein present in large dense core vesicles of neuroendocrine cells. Despite being long identified as the most useful NEN-related circulating marker, clinical application of CgA is controversial. CgA assays still lack standardization, thus hampering not only clinical management but also the comparison between different analyses. In the diagnostic setting, clinical utility of CgA is limited as hampered by (a) the variety of oncological and non-oncological conditions affecting marker levels, which impairs specificity; (b) the fact that 30-50% of NENs show normal CgA, which impairs sensitivity. Regarding the prognostic phase, there is prospective evidence which demonstrates that advanced NENs secreting CgA have poorer outcome, as compared with those showing non-elevated marker levels. Although the identification of cut-offs allowing a proper risk stratification of CgA-secreting patients has not been performed, this represents the most important clinical application of the marker. By contrast, based on prospective studies, the trend of elevated circulating CgA does not represent a valid indicator of morphological evolution and has therefore no utility for the follow-up phase. Ultimately, current knowledge about the role of the marker for the definition of treatment strategy is poor and is limited by the small number of available studies, their prevalent retrospective nature and the absence of control groups of untreated subjects.

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Section: Resultsmentioning

confidence: 99%

Section: Baseline Cga As Predictive Marker Of Treatment Efficacymentioning

confidence: 88%

Section: Circulating Cga As a Prognostic Marker In Nenmentioning

confidence: 99%

See 1 more Smart Citation

Chromogranin A as circulating marker for diagnosis and management of neuroendocrine neoplasms: more flaws than fame

Marotta

Zatelli

Sciammarella³

et al. 2018

Endocrine-Related Cancer

125

104

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“…The results of the RADIANT trial series[20–23] and sub-analyses[59–71] are summarized in Table 1. The efficacy of everolimus in NETs was initially investigated in the RADIANT-1 trial, an open-label, phase II pilot dose-finding study involving patients with metastatic, low- to intermediate-grade NETs of pancreas, small bowel, and lung origin[20].…”

Section: Efficacy Of Everolimusmentioning

confidence: 99%

“…This result may have been affected by the imbalance of patient characteristics between the everolimus and the control arms (i.e., WHO performance status, lung origin). Several sub-group analyses were performed from the results of the RADIANT-2 trial (Table 1)[59–64]. Although the numbers were small, everolimus plus octreotide demonstrated superior anti-tumor activity in patients with lung[60] and colorectal NETs[61].…”

Section: Efficacy Of Everolimusmentioning

confidence: 99%

Everolimus in the treatment of neuroendocrine tumors: efficacy, side-effects, resistance, and factors affecting its place in the treatment sequence

Lee

Ito

Jensen

2018

Expert Opinion on Pharmacotherapy

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Introduction: Since the initial approval of everolimus in 2011, there have been a number of important changes in therapeutic/diagnostic modalities as well as classification/staging systems of neuroendocrine tumors (NETs), which can significantly impact the use of everolimus in patients with advanced NETs. Areas covered: The efficacy of everolimus monotherapy and combination therapy demonstrated in clinical studies involving patients with advanced NETs are reviewed. Several factors affecting everolimus’ use are described including: the development and routine use of NET classification/staging systems; widespread use of molecular imaging modalities; side-effects; drug resistance; and the availability of other treatment options. Furthermore, the current position of everolimus in the treatment approach is discussed, taking into account the recommendations from the recent guidelines. Expert opinion: Although everolimus demonstrated its high efficacy and tolerability in the RADIANT trials and other clinical studies, there still remain a number of controversies related to everolimus treatment in the management of NETs. The synergistic anti-growth effect of other agents in combination with everolimus or its effect on overall survival have not been established. The appropriate order of the use of everolimus in the treatment of advanced NETs still remains unclear, which needs to be defined in further studies and will be addressed in the new guidelines.

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Treatment for gastrointestinal and pancreatic neuroendocrine tumours: a network meta-analysis

Walter

Nesti

Spanjol

et al. 2021

Cochrane Database of Systematic Reviews

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Efficacy of everolimus plus octreotide LAR in patients with advanced neuroendocrine tumor and carcinoid syndrome: final overall survival from the randomized, placebo-controlled phase 3 RADIANT-2 study

Abstract: NCT00412061, www.clinicaltrials.gov.

Cited by 97 publications

References 9 publications

Chromogranin A as circulating marker for diagnosis and management of neuroendocrine neoplasms: more flaws than fame

Chromogranin A as circulating marker for diagnosis and management of neuroendocrine neoplasms: more flaws than fame

Everolimus in the treatment of neuroendocrine tumors: efficacy, side-effects, resistance, and factors affecting its place in the treatment sequence

Treatment for gastrointestinal and pancreatic neuroendocrine tumours: a network meta-analysis

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