Pazopanib Shows Advanced Pancreatic NET Promise

A multitargeted kinase inhibitor against vascular endothelial growth factor receptors 1, 2 and 3 may benefit patients with advanced neuroendocrine tumours

medwireNews: Patients with locally advanced or metastatic well-differentiated pancreatic neuroendocrine tumours (NETs) may benefit from the addition of pazopanib to depot octreotide, suggest phase II results published in The Lancet Oncology.

Seven (21.9%) of the 32 pancreatic NET patients given pazopanib 800 mg once daily achieved an objective response, defined as at least a 30% reduction in the sum of the longest diameters for up to five target lesions.

By contrast, none of the 20 patients with grade 1 or 2 carcinoid tumours achieved an objective response and accrual of these patients to the trial was halted.

Fatigue, nausea, diarrhoea and hypertension were the most common side effects, affecting 39, 33, 33 and 28, respectively, of the 52 patients treated. Aminotransferase elevations and neutropenia were the most common grade 3 toxicities, each reported in three patients, while grade 4 events of thrombosis and hypertriglyceridaemia occurred in one patient each.

“Further studies to assess the role of pazopanib in the management of both pancreatic and extrapancreatic NETs are warranted”, write James Yao, from University of Texas MD Anderson Cancer Center in Houston, USA, and co-authors.

A phase II randomised study of pazopanib versus placebo in patients with progressive NET is ongoing, while a phase III study comparing the agent against best supportive care for patients who have failed targeted treatment is now planned, they say.

But progression-free survival may be a better endpoint than radiographical response for patients with carcinoid tumours, the authors suggest.

DikKwekkeboom, from Erasmus Medical Center in Rotterdam, the Netherlands, notes in an accompanying comment that everolimus and sunitinib have also been shown to be effective for pancreatic NETs but not carcinoids, and the two tumour types should therefore be “regarded as separate clinical entities.”

Six of the seven NET patients with objective responses had disease progression at baseline, he observes.

Recognising that pazopanib has previously been shown to be effective in renal cell carcinoma patients with disease progression on other vascular endothelia growth factor Receptor inhibitors, he writes: “If this finding is also true for patients with pancreatic NETs, this drug could be a true addition to the range of effective drugs available for these patients.”

References

Phan AT, Halperin DM, Chan JA, et al. Pazopanib and depot octreotide in advanced, well-differentiated neuroendocrine tumours: a multicentre, single-group, phase 2 study. Lancet Oncol; Advance online publication 5 May 2015. dx.doi.org/10.1016/S1470-2045(15)70136-1

Kwekkeboom DJ. Pazopanib: a new drug for pancreatic neuroendocrine tumours. Lancet Oncol; Advance online publication 5 May 2015. dx.doi.org/10.1016/S1470-2045(15)70200-7

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