Promising but inconclusive results for everolimus in advanced pancreatic NET

Last Updated: 2016-10-13

By Will Boggs MD

NEW YORK (Reuters Health) - A new report stokes hopes that everolimus may prolong survival in patients with advanced pancreatic neuroendocrine tumors (NETs), but offers no clear answers.

Based on these findings as well as "recent results from RADIANT4 published in Lancet, everolimus is broadly efficacious in advanced neuroendocrine tumors," Dr. James C. Yao from the University of Texas MD Anderson Cancer Center in Houston told Reuters Health by email. "It should be considered standard of care in progressive NETs."

Pancreatic NET is usually detected at an advanced stage, Dr. Yao and colleagues note in the Journal of Clinical Oncology, online September 12. Everolimus, an oral inhibitor of mammalian target of rapamycin, significantly prolonged median progression-free survival by 6.4 months in patients in RADIANT-3.

Now, the researchers report final overall survival data and safety information for RADIANT-3, which included 410 patients with advanced pancreatic NET.

Median overall survival was 44.0 months among patients randomized to everolimus, compared to 37.7 months among patients in the placebo group (hazard ratio, 0.94; p=0.30), many of whom were switched subsequently to open-label everolimus.

This compares with median survival around 27 months in previous reports.

After correcting for crossovers, the 12- and 24-month survival rates were 82.6% and 67.7%, respectively, in the everolimus arm and 74.9% and 55.6% in the placebo arm (HR, 0.60; 95% confidence interval, 0.09 to 3.95).

Lower baseline levels of neuron-specific enolase (NSE) and placental growth factor (PIGF) were significantly associated with better overall survival in a multivariable analysis of seven biomarkers.

There were no new safety concerns. Study drug discontinuation due to adverse events was more common with everolimus (21.1%) than with placebo (5.9%) in the double-blind phase.

"The field of NETs has seen significant advances in the recent years," Dr. Yao said. "Working together, we can apply rigorous clinical trial methodology and make real progress in even rare diseases."

Dr. Emilio Bertani from the European Institute of Oncology in Milan, Italy, told Reuters Health by email, "The overall survival of 44 months among patients treated with everolimus is remarkable and could be a benchmark for future studies. I personally consider very important also the fact that no new safety profile findings were observed during this study."

"Everolimus may (have a) place in the treatment algorithm of progressing metastatic and/or unresectable pancreatic NETs competing with sunitinib and peptide receptor radionuclide therapy (PRRT) since these latter therapies showed promising results in the same setting of patients," he said.

"Advanced progressing pancreatic NET is a curable disease and everolimus may be safely used to prolong survival in these patients," Dr. Bertani said. "I personally advocate randomized studies comparing everolimus, sunitinib, and PRRT to better define the treatment algorithm for patients with progressing advanced pancreatic NETs. Another key point is the potential role of surgery (i.e., primary tumor resection, when feasible) before or after such treatments."

SOURCE: http://bit.ly/2cE91JT

J Clin Oncol 2016.