Sunitinib in pancreatic neuroendocrine tumors: updated progression-free survival and final overall survival from a phase III randomized study

Faivre, Sandrine; Niccoli, Patricia; Castellano, Daniel; Valle, Juan W.; Hammel, Pascal; Raoul, Jean‐Luc; Vinik, Aaron I.; Cutsem, Éric Van; Bang, Yung‐Jue; Lee, S.-H.; Borbath, Ivan; Lombard‐Bohas, Catherine; Metrakos, Peter; Smith, Denis; Chen, J.-S.; Ruszniewski, Philippe; Seitz, Jean‐François; Patyna, Shem; Lu, Dongrui R.; Ishak, K. Jack; Raymond, Éric

doi:10.1093/annonc/mdw561

Cited by 152 publications

(138 citation statements)

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“…The trial was terminated early after a higher number of serious adverse events (SAEs) and deaths were observed in the placebo arm compared with the sunitinib arm, and a difference in investigator-assessed PFS favoured sunitinib (hazard ratio [HR], 0.42, 95% confidence interval [CI], 0.26-0.66; p < 0.001; median 11.4 [7.4-19.8] vs. 5.5 [3.6-7.4] months) [5]. Five years after study closure, median (95% CI) overall survival (OS) was 38.6 (25.6-56.4) and 29.1 (16.4-36.8) months (HR, 0.73; 95% CI, 0.50-1.06; p = 0.094) with sunitinib and placebo, respectively; the lack of significance was probably due to the crossover, in which 69% of patients had switched from placebo to sunitinib [6].…”

Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Sunitinib in Patients with Well-Differentiated Pancreatic Neuroendocrine Tumours

et al. 2018

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Background: In a phase III study, sunitinib led to a significant increase in progression-free survival (PFS) versus placebo in patients with pancreatic neuroendocrine tumours (panNETs). This study was a post-marketing commitment to support the phase III data. Methods: In this ongoing, open-label, phase IV trial (NCT01525550), patients with progressive, advanced unresectable/metastatic, well-differentiated panNETs received continuous sunitinib 37.5 mg once daily. Eligibility criteria were similar to those of the phase III study. The primary endpoint was investigator-assessed PFS per Response Evaluation Criteria in Solid Tumours v1.0 (RECIST). Other endpoints included PFS per Choi criteria, overall survival (OS), objective response rate (ORR), and adverse events (AEs). Results: Sixty-one treatment-naive and 45 previously treated patients received sunitinib. By March 19, 2016, 82 (77%) patients had discontinued treatment, mainly due to disease progression. Median treatment duration was 11.7 months. Investigator-assessed median PFS per RECIST (95% confidence interval [CI]) was 13.2 months (10.9–16.7): 13.2 (7.4–16.8) and 13.0 (9.2–20.4) in treatment-naive and previously treated patients, respectively. ORR (95% CI) per RECIST was 24.5% (16.7–33.8) in the total population: 21.3% (11.9–33.7) in treatment-naive and 28.9% (16.4–44.3) in previously treated patients. Median OS, although not yet mature, was 37.8 months (95% CI, 33.0–not estimable). The most common treatment-related AEs were neutropenia (53.8%), diarrhoea (46.2%), and leukopenia (43.4%). Conclusions: This phase IV trial confirms sunitinib as an efficacious and safe treatment option in patients with advanced/metastatic, well-differentiated, unresectable panNETs, and supports the phase III study outcomes. AEs were consistent with the known safety profile of sunitinib.

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Section: Introductionmentioning

confidence: 99%

Efficacy and Safety of Sunitinib in Patients with Well-Differentiated Pancreatic Neuroendocrine Tumours

et al. 2018

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“…Noteworthy, in none of these trials a significant OS benefit was demonstrated. [8][9][10][11][12][13][14][15] Conclusion: To date, published trials are comparable in design and efficacy, and the corresponding MCBS-FT score of 2-3 is consistent with the moderate clinical benefit seen while treating patients with advanced or metastatic NET. The fact that all trials rated equally in quite similar clinical settings reflects however one difficulty of the scale in its current version: as only one trial may be considered at once (except for meta-analyses), there is no additional information for optimal sequencing of treatment options added by the ESMO-MCBS scoring system; this has also previously been discussed for colorectal cancer and renal cell cancer in our pilot analysis.…”

Section: Results Neuroendocrine Tumoursmentioning

confidence: 53%

“…[8][9][10][11][12][13][14][15] Assessment of ESMO-MCBS scores for advanced NET revealed comparable results in all available data (all trials placebo controlled). The CLARINET and the PROMID trial represent two proof of principle studies demonstrating for the first time direct antiproliferative effects of somatostatin analogues for advanced midgut and pancreatic NET irrespective of progression status.…”

Section: Results Neuroendocrine Tumoursmentioning

confidence: 76%

“…In NETs, for example, all current trials resulted in a MCBS-FT score of 2 or 3 reflecting the moderate PFS benefit aligned with a favourable toxicity profile quintessential for the treatment of this specific disease. [8][9][10][11][12][13][14][15] However, a maximum score of 3 is clearly inferior to results achieved for metastatic breast or colorectal Kiesewetter cancer. 5 This fact might possibly be related to the inferior power of trials in infrequent diseases.…”

Section: Discussionmentioning

confidence: 89%

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The European Society for Medical Oncology 'Magnitude of Clinical Benefit Scale' field-tested in infrequent tumour entities: an extended analysis of its feasibility at the Medical University of Vienna

et al. 2017

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BackgroundThe European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) is a new tool to quantify the clinical benefit that may be anticipated from a novel anticancer treatment. We present here an analysis on the feasibility of the ESMO-MCBS in less frequent tumour entities.MethodsThis study evaluates the practicability of the ESMO-MCBS for metastatic neuroendocrine tumours (NETs), soft tissue sarcomas, glioblastoma, thyroid cancer, pancreatic cancer, head/neck cancer, urothelial cancer and ovarian cancer at the Medical University Vienna. A three-step approach including data acquisition, assessment of ESMO-MCBS scores and evaluation of results with a focus on clinical feasibility was applied.ResultsIn NET and thyroid cancer, all analysed trials were very comparable in design and efficacy, and the ESMO-MCBS scores appeared to be consistent with the clinical benefit seen in practice. For pancreatic cancer, it was more difficult to compare first-line trials due to diverging populations included in the respective studies. Concerning soft tissue sarcomas, the ESMO-MCBS was applicable for gastrointestinal stromal tumours(GIST) and ‘non-GIST’ soft tissue sarcoma with respect to data deriving from randomised studies. However, due to the heterogeneity of the disease itself and a limited number of controlled trials, limitations are noted. In ovarian cancer, the ESMO-MCBS supported the use of bevacizumab in high-risk patients. To date, there are only limited data for glioblastoma, head/neck cancer and urothelial cancer but whenever randomised trials were available, the ESMO-MCBS rating supported clinical decisions. Interestingly, nivolumab for salvage treatment of head/neck cancer rated extremely high.ConclusionThe ESMO-MCBS scores supported our common treatment strategies and highlight the potential of new immunomodulatory drugs. Our results encourage further development of the ESMO-MCBS.

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“…Sunitinib is an oral, smallmolecule, multi-targeted tyrosine kinase inhibitor with activity against VEG-F and PDGF. A recent phase III trial randomized 171 patients with advanced well differentiated pNENs compared therapy with sunitinib versus placebo (65). The study was discontinued early because of the clear advantage of sunitinib versus the placebo group.…”

Section: Agents For Antiangiogeneismentioning

confidence: 99%

Pancreatic neuroendocrine tumors

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2017

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Sunitinib in pancreatic neuroendocrine tumors: updated progression-free survival and final overall survival from a phase III randomized study

Abstract: NCT00428597.

Cited by 152 publications

References 14 publications

Efficacy and Safety of Sunitinib in Patients with Well-Differentiated Pancreatic Neuroendocrine Tumours

Efficacy and Safety of Sunitinib in Patients with Well-Differentiated Pancreatic Neuroendocrine Tumours

The European Society for Medical Oncology 'Magnitude of Clinical Benefit Scale' field-tested in infrequent tumour entities: an extended analysis of its feasibility at the Medical University of Vienna

Pancreatic neuroendocrine tumors

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