Octreotide LAR extends survival in low hepatic load neuroendocrine tumors

Octreotide LAR not only prolongs time to progression (TTP) but also appears to extend overall survival (OS) in a subgroup of patients with metastatic midgut neuroendocrine tumors (NETs) and a low hepatic load.

“A trend in longer survival in this subgroup is further indication to give octreotide LAR immediately upon diagnosis. The drug should be started as early as possible for these patients,” said Rudolf Arnold, MD, professor of gastroenterology at Phillips University Marburg, in Marburg, Germany, at the American Society of Clinical Oncology annual meeting in Chicago.

Previously, octreotide LAR had shown to lengthen significantly TTP in patients with metastatic midgut NET in the PROMID trial, a placebo-controlled, double blind, prospective, randomized study. The anti-proliferative response was more pronounced in patients with low (≤10%) hepatic tumor load, said Dr Arnold. This follow-up study investigated whether this beneficial effect also affects OS.

The new study included 85 patients from the PROMID trial who were followed at least once a year for 7 years. The patients were randomly assigned to receive octreotide LAR (42 patients) or placebo (43 patients). Post-study treatment was left at the discretion of the local investigator. If patients progressed on placebo, they crossed over to octreotide.

Of the 85 patients, 19 died in the octreotide arm and 22 died in the placebo arm. Median OS was not reached in the treatment arm and was 84 months in the placebo arm (P=.59, HR=0.85). In the low hepatic tumor load subgroup of 64 patients, median OS was not reached in the octreotide group versus 80.5 months in the placebo group (P=.14, HR=0.56). TTP was not prolonged in the high (HL>10%) subgroup.

Dr Arnold noted that placebo patients were allowed to cross over to the treatment arm and that may have influenced the OS benefit. “If we wait longer, we might see a statistically significant difference in OS. In this interim analysis, we saw a trend in favor of longer survival. If patients survive longer, they should receive the active drug sooner,” he said.

He added: “I believe that newly diagnosed patients should immediately receive octreotide LAR. If there is a survival benefit, then a watch-and-wait strategy is not possible.” Dr Arnold noted that “everyone in the placebo group progressed within 30 months. There is no stabilization of disease. If they all progress, why not treat them immediately?”

There was also a difference between the 2 arms initially. The octreotide LAR arm had a longer time since diagnosis, which might indicate they had more indolent disease.

In conclusion, Dr Arnold said “almost all patients who were randomized at study entry in the placebo group received octreotide LAR after disease progression, but these patients experienced a less favorable OS than those in the low hepatic load subgroup.”

ASCO discussant Abby Siegel, MD, medical director of Hepatobiliary Oncology at New York-Presbyterian Hospital/Columbia University Medical Center in New York, commented: “Octreotide LAR is still the standard of care for NETs. Interestingly, the OS of the placebo arm was about 7 years, with the median OS not yet reached in the treatment arm. This gives us a benchmark for our patients.” 

Dr Arnold has received honoraria from Novartis, as have several of his collaborators.