Expert Point of View: Enrique Grande, MD

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Enrique Grande, MD

Despite the encouraging activity of everolimus, we don’t have the full picture yet.

—Enrique Grande, MD

Enrique Grande, MD, Head of the Endocrine and Genitourinary Tumors Section of the Medical Oncology Service at Ramon y Cajal University Hospital, Madrid, discussed the NETTER-1 and RADIANT-4 studies at the Presidential Session of the 2015 European Cancer Congress.

“There is now a stronger rationale behind the use of everolimus (Afinitor) as a single agent after failure on [somatostatin analogs], regardless of the primary tumor origin,” he said, “and lutetium Lu-177 dotatate plus [a somatostatin analog] might become a standard in progressive midgut [neuroendocrine tumors].”

Qualifying Remarks

Dr. Grande noted that everolimus is the first drug to show, in a randomized trial, significant activity in lung neuroendocrine tumors (hazard ratio [HR] = 0.50), but he questioned whether the primary endpoint, in the context of other neuroendocrine tumor trials, was actually that impressive.

Acknowledging the danger in cross-trial comparisons and extrapolations, he indicated, “The median progression-free survival of 11 months with everolimus is not better than with [somatostatin analogs] alone,” as was shown in RADIANT-2.

“Despite the encouraging activity of everolimus, we don’t have the full picture yet,” he continued. Other questions pertain to the benefit in patients with functioning tumors and in patients with a good prognosis, who gained little to nothing from everolimus in RADIANT-4.

‘Impressive Cohort’

Turning to the NETTER-1 trial, Dr. Grande predicted, “Peptide receptor radionuclide therapy is here to stay.” The Lu-177 dotatate cohort, he said, is “the most impressive cohort we have seen in the [neuroendocrine tumor] field, in terms of hazard ratio for progression-free survival,” especially since the trial’s comparator arm was an active regimen.

“We have a new mode of action, using an old, classic target in [neuroendocrine tumors],” he concluded. “NETTER-1 confirms the activity of [peptide receptor radionuclide therapy] found in midgut [neuroendocrine tumor] retrospective series.”

Whether the findings can be extrapolated to nonmidgut neuroendocrine tumors remains unanswered, and its long-term safety profile has not been shown. Furthermore, there may be logistical concerns, he said, including “how to request the compound, how to produce the compound, how to deliver the compound to our institutions, and how to administer it.”

“In spite of its high activity,” he concluded, “I am not sure how available this drug will be for our patients.”   ■

Disclosure: Dr. Grande has been an advisor for IPSEN, Lexicon, Pfizer, and Novartis.

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