A randomized, open-label, phase 2 study of everolimus in combination with pasireotide LAR or everolimus alone in advanced, well-differentiated, progressive pancreatic neuroendocrine tumors: COOPERATE-2 trial

Abstract

The addition of pasireotide to everolimus was not associated with the improvement in PFS compared with everolimus alone in this study. Further studies to delineate mechanisms by which SSAs slow tumor growth in NET are warranted.

Sequential Everolimus and Sunitinib Treatment in Pancreatic Metastatic Well-Differentiated Neuroendocrine Tumours Resistant to Prior Treatments

“…In one of these trials, everolimus was explored in combination with the novel SSA pasireotide, an upstream activator of the mTOR pathway without any benefit in the PFS [24] . Another trial investigated the combination of everolimus and the angiogenesis inhibitor bevacizumab that binds circulating VEGF compared to everolimus alone [25] .…”

NeuroEndocrine Tumor Therapy with Lutetium-177-octreotate and Everolimus (NETTLE): A Phase I Study

“…17 Everolimus combined with the long-acting somatostatin analog pasireotide LAR was evaluated in a phase II randomized controlled trial in 160 patients with advanced progressive PNETs in the multinational COOPERATE-2 study, which reported a median PFS of 16.8 months versus 16.6 months for everolimus alone. 18 The objective response showed PR advantage for the combination (20.3% vs. 6.2%), but stabilization of disease was comparable in the two groups. Grade 3/4 toxicity in respect of fasting hyperglycemia was increased in the combination group (37% vs. 11%).…”

“…Grade 3/4 toxicity in respect of fasting hyperglycemia was increased in the combination group (37% vs. 11%). 18 Contemporary clinical investigation of molecular targeted therapeutics may overlook agents that work most effectively in combination with radiation. 12 Co-development of innovative drug combinations with radionuclide therapy, such as that explored in our phase IB study of 177 Lu-octreotate PRRT and everolimus, directed simultaneously at multiple therapeutic targets, has the potential to improve the response to treatment.…”

WOMEN IN CANCER THEMATIC REVIEW: Systemic therapies in neuroendocrine tumors and novel approaches toward personalized medicine

“…In one of these trials, everolimus was explored in combination with a novel somatostatin analogue, pasireotide that binds to four of five somatostatin receptors and downregulates IGF-1, an upstream activator of the mTOR pathway (Kulke et al 2015c). Another trial investigated the combination of everolimus and an angiogenesis inhibitor, bevacizumab, which binds circulating VEGF (Kulke et al 2015b).…”