Lutathera improves outcomes in metastatic midgut neuroendocrine tumors

Issue: February 25, 2016

Treatment with ¹⁷⁷Lutetium-DOTATE appeared to improve the overall response rate and prolonged PFS compared with octreotide among previously treated patients with advanced midgut neuroendocrine tumors, according to early results from the phase 3 NETTER-1 trial presented at the Gastrointestinal Cancers Symposium.

Perspective from Vincent J. Picozzi, MD

Further, ¹⁷⁷Lutetium-DOTATE (Lutathera, Advanced Accelerator Applications) therapy demonstrated a trend toward improved OS.

Jonathan R. Strosberg

“The 79% improvement in PFS is the largest that we have seen in a randomized neuroendocrine tumor trial,” Jonathan R. Strosberg, MD, medical oncologist at Moffitt Cancer Center, told HemOnc Today. “Moreover, there is a very strong suggestion of improvement in OS with 22 deaths on the octreotide arm vs. only 13 with Lutathera. The safety profile of the drug is highly favorable.”

The agent is part of a new class of drugs known as peptide receptor radionuclide therapy, which combines radiotherapy and hormone therapy. In ¹⁷⁷Lutetium-DOTATE, a somatostatin analog attaches to a radioactive molecule, allowing for targeted delivery of radiation to the tumor.

Patients with metastatic midgut neuroendocrine tumors usually receive hormone therapy with a somatostatin analog, such as octreotide or lanreotide.

Because there are currently no effective second-line treatment options for patients with tumors that stop responding to somatostatin analogs, Strosberg and colleagues sought to compare ¹⁷⁷Lutetium-DOTATE to octreotide LAR in patients with inoperable and progressive disease.

By February 2015, the investigators identified 230 patients from 51 international sites with grade 1 or grade 2 metastatic midgut neuroendocrine tumors and randomly assigned them (1:1) to receive four administrations of ¹⁷⁷Lutetium-DOTATE (7.4 GBq) every 8 weeks or octreotide LAR (60 mg) every 4 weeks.

PFS served as the primary endpoint of the study. Secondary endpoints included objective response rate (ORR), OS, toxicity and quality of life.

At the time of the analysis, there were 23 confirmed disease progressions or deaths in the experimental arm vs. 67 in the control arm.

The median PFS was not reached for ¹⁷⁷Lutetium-DOTATE — although researchers are estimating that it will reach 40 months, Strosberg said — and was 8.4 months (95% CI, 5.8-11 months) in the octreotide arm (HR = 0.21; 95% CI, 0.13-0.34).

A total of 201 patients remained evaluable for tumor response. Of this group, there were 10 partial or complete responses (18%) among those who received ¹⁷⁷Lutetium-DOTATE vs. three (3%) in the control group (P < .0008).

“That 18% is a pretty impressive number since these tumors are typically unresponsive to systemic therapy,” Strosberg said during a press briefing. “Those numbers are usually in the single digits.”

OS data were not mature at the time of analysis; however, there were 13 deaths in the experimental group and 22 in the octreotide group, which indicates a trend toward improvement in OS (P < .019 at interim analysis).

“The new therapy is … more convenient — it requires only four treatments, as opposed to medications that patients have to take daily over long periods of time,” Strosberg said. “Based on this trial, we hope that Lutathera will be FDA approved and available for treatment of patients in the United States in 2016.” – by Anthony SanFilippo

Reference:

Strosberg JR, et al. Abstract 194. Presented at: Gastrointestinal Cancers Symposium; Jan. 21-23, 2016; San Francisco.

For more information:

Jonathan R. Strosberg, MD, can be reached at jonathan.strosberg@moffitt.org.

Disclosure: This study was funded by Advanced Accelerator Applications (AAA). Strosberg reports no relevant financial disclosures. Two other researchers report consultant/advisory roles with, stock or other ownership in and research funding from AAA, Genentech/Roche, Guardant Health, Ipsen, Lexicon, Merck, Merrimack, Novartis and Pharm-Olam.

Perspective

Vincent J. Picozzi, MD

The presentation by Strosberg and colleagues from the Moffitt Cancer Center in Tampa, Florida, is of particular interest and particular import to clinicians. This was a comparison in over 200 patients of a radioactive form of octreotide, in which it was compared with standard form of octreotide used to treat patients with midgut neuroendocrine cancers. This is a treatment that’s been tested in Europe over the past few years. It’s just now coming to the United States for testing.

In this rather large trial, which involved over 200 patients, there was a striking difference in the disease control and time to progression using the radioactive compound as opposed to the standard compound.

This, I believe, presents an exciting new option for therapy for around the world, but particularly here in the US. The hope is that this agent can be licensed in the near future and be made available to our patients here.

Vincent J. Picozzi, MD

Virginia Mason Medical Center

Disclosures: Picozzi reports stock and ownership interests in AbbVie, Amgen and Johnson & Johnson; honoraria from Celgene; consulting or advisory roles for Halozyme and Taiho Pharmaceutical; and research funding from Aduro Biotech, Clovis Oncology, FibroGen, Immunomedics, Incyte, OncoMed and Theranostics Health.