'Most Impressive' PFS Ever Seen in Midgut NET

Zosia Chustecka

September 28, 2015

VIENNA — Patients with midgut neuroendocrine tumors (NETs) who progress on standard treatment with the somatostatin analogue octreotide have few treatment options, but they may soon have a new one — a radiopharmaceutical that appears to deliver a very long-lasting benefit.

The investigative radiopharmaceutical "appears to be a major advance" for this patient population, said the lead investigator Philippe Ruszniewski, MD, head of gastroenterology-pancreatology at Beaujon Hospital in Clichy, France.

Dr Philippe Ruszniewski

The product achieved "the most impressive progression-free survival we have ever seen" in such patients, said discussant for the study, Enrique Grande, MD, from the Department of Medical Oncology at Ramón y Cajal University Hospital in Madrid.

Both were speaking here at a presidential session at the European Cancer Congress 2015.

The radiopharmaceutical is 177Lu-DOTATATE (Lutathera, under development by Advanced Accelerator Applications). It is a lutetium-labeled octreotate, which is a derivative of octreotide, and Dr Grande described it as having a new mode of action but acting on an old classic target.

The data come from a phase 3 trial known as the NETTER-1 study, conducted in 230 patients with advanced midgut NET who had already been treated with somatostatin analogues. Most patients were metastatic, Dr Ruszniewski said that almost all had liver metastases, and most also had lymph node metastases.

All patients received the standard of care, long-acting release (LAR) octreotide, and were randomized 1:1 to also receive the radiopharmaceutical (7.4 GBq given intravenously every 8 weeks for four doses). Patients who also had the radiopharmaceutical received octreotide LAR at 30 mg every 4 weeks, while those in the control group had a double dose, receiving 60 mg every 4 weeks; this product is administered by deep intragluteal injection.

"Results so far show that patients on Lutathera are achieving extra time without their disease progressing," Dr Ruszniewski said at a press briefing.

The number of centrally confirmed disease progressions or deaths was 23 in the radiopharmaceutical group and 67 in the control group.

Progression-free survival is significantly longer in the patients who received the radiopharmaceutical in addition to octreotide LAR, with a hazard ratio of 0.2 (P < .001), which translates to an 80% reduction in the risk for disease progression or death. The median progression-free survival is 8.4 months (95% confidence interval, 5.8 - 11.0 months) in patients who received octreotide alone, but the median has not yet been reached in the radiopharmaceutical group. Dr Ruszniewski told Medscape Medical News that it was estimated at around 40 months.

"This kind of PFS is rarely seen in cancer," he commented.

The overall response rate was also much better, with one complete response (CR) and 18 partial responses (PRs) seen with the radiopharmaceutical compared with no CRs and three PRs in the control group.

Overall survival data are not mature, but so far there have been 13 deaths in the radiopharmaceutical group and 22 in the octreotide group, he noted.

Dr Ruszniewski said that the radiopharmaceutical had a "good' safety profile, and that it offers patients a good quality of life. He reported that serious treatment-related adverse events were reported by 26% in the radiopharmaceutical group and 24% in the control group. Among the adverse events reported with the radiopharmaceutical were lymphocytopenia and thrombocytopenia, and there was one acute kidney failure.

In his discussion, Dr Grande said that long-term data were need on safety, especially in view of the cytopenias that were reported.

Dr Grande also expressed concern over the logistics of how the radiopharmaceutical would be used. How would a clinician request this product, where would it be administered, etc? He wondered if the radiopharmaceutical could be made widely available.

Another radiopharmaceutical, radium-223 (Xofigo, Algeta/Bayer), which is approved for prostate cancer, has some very impressive data, but the product is not used as much as other agents that are given orally that were approved at around the same time.

But Dr Ruszniewski argued that the fact that it is a radiopharmaceutical may be an advantage, especially in terms of allocating healthcare resources. Patients who are eligible for treatment with the radiopharmaceutical, and who should respond positively to it, can be identified by scintigraphy, as previously reported by Medscape Medical News. This should ensure that most patients who receive this product are likely to respond, which "should lead to substantial savings," he said.

He expressed hope that the radiopharmaceutical would be approved soon by regulatory authorities, and said it should now be tested in other types of NET, for example pancreatic and bronchial NET.

Commenting on the study, Peter Naredi, MD, PhD, scientific cochair of the Congress, said the researchers should be congratulated on this achievement. "Midgut NET is a rare disease and to perform randomized phase 3 trials necessitates a joint effort by many investigators." He added that the "positive outcome from this study will most likely influence clinical practice."

The study was funded by Advanced Accelerator Applications, the manufacturer of Lutathera. Dr Ruszniewski has disclosed no relevant financial relationships.

European Cancer Congress (ECC) 2015: Abstract LBA6. Presented September 27, 2015.


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