"So I have some concerns about the benefit of everolimus," said Dr. Mulcahy of the Robert H. Lurie Comprehensive Cancer Center in Chicago. "For the population studied, I think the benefit of everolimus with octreotide LAR is undefined. The activity of everolimus is demonstrated, but it’s associated with significant adverse events."
RADIANT-3: Pancreatic NET
The RADIANT-3 trial was conducted among 410 patients with progressive advanced pancreatic NET (pNET). It found a 65% reduction in the risk of progression with everolimus plus best supportive care, compared with placebo plus best supportive care (HR 0.35, P less than .0001).
Updated analyses showed that the benefit seen in the whole study population was also evident in subgroups stratified by patient and disease factors, and prior treatment, reported lead investigator Dr. Manisha H. Shah of the Ohio State University Comprehensive Cancer Center in Columbus.
"No matter how we slice the data based on different characteristics, we saw the significant benefit of everolimus compared to placebo," she commented. Some 50% of the patients had previously used somatostatin analogs, and 40% of patients used these agents concomitantly while in the trial.
In exploratory analyses, the progression-free survival benefit of everolimus was similar in subgroups of patients who had and had not previously used somatostatin analogs, and who did and did not use them concomitantly during the trial.
"Everolimus showed a consistent benefit in all subgroups regardless of presence or absence of somatostatin analog," commented Dr. Shah.
"RADIANT-3 is the largest randomized controlled trial ever completed in patients with progressive advanced pNET," she noted. "These data support the use of everolimus as the standard of care for patients with progressive advanced pNET."
In her discussion, Dr. Mulcahy noted that, in this trial, results were similar for central and local review. "That’s probably because these patients did not necessarily have the secretory symptoms of the patients in the RADIANT-2 study," she speculated.
The results are "strikingly similar" to those seen previously with the tyrosine kinase inhibitor sunitinib (Sutent) in patients with pNET. "We are seeing consistent results. How we are going to sequence these is something that needs to be further evaluated."
Her overall assessment of RADIANT-3 was more positive than that of RADIANT-2. "There is a significant and durable benefit of everolimus in previously treated [pNET] patients," she commented.
A variety of markers are being assessed in NET, including some associated with response to mTOR inhibitors, according to Dr. Mulcahy.
"This is hopefully the direction where we are going to be going, looking at these different prognostic and predictive markers, and assigning therapy and doing rationally designed clinical trials to find the best sequence of drugs," she concluded.
Novartis sponsored both trials. Dr. Yao and Dr. Shah reported being advisors to and receiving honoraria and research support from Novartis. Dr. Mulcahy did not report any relevant conflicts of interest.