Treatment Sequencing and Combinations in pNETs

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Several factors contribute to the decision-making process when treating patients with pancreatic neuroendocrine tumors (pNETs), Jonathan R. Strosberg, MD, describes. Everolimus or sunitinib should be considered in patients with mild symptoms or relatively extensive disease who have no evidence of high proliferation activity or imminent danger. For somatostatin analog naïve patients, Strosberg believes octreotide or lanreotide can safely be added to the targeted therapies, further prolonging time to progression. However, this approach has not been validated in clinical trials.

For patients with functional hormone secreting tumors, Diane Reidy-Lagunes, MD, MS, generally administers a somatostatin analog in the frontline setting, sometimes in combination with a targeted therapy. The level of disease burden is important to consider, since the combination may not be needed in non-functional tumors. Additionally, if a patient slowly progresses on single-agent somatostatin analog, treatment with this agent can be continued with the addition of a targeted therapy, Reidy-Lagunes suggests.

Rodney F. Pommier, MD, comments that the COOPERATE-2 clinical trial is underway, which is examining the use of everolimus alone or in combination with the somatostatin analog pasireotide long-acting release (LAR) in patients with progressive advanced or unresectable pNETs. Pasireotide LAR has a different affinity and binding profile than does octreotide or lanreotide. The available evidence suggests octreotide and lanreotide are somewhat interchangeable, says Strosberg.

In terms of efficacy, everolimus and sunitinib are similar, as are octreotide and lanreotide, making a treatment selection difficult. To answer the question of which therapy to use, the side effect profiles are usually what guide the treatment decision, Reidy-Lagunes notes.