The approval last week of a novel radiaopharmaceutical to treat a group of rare cancers provides a new option for patients with these malignancies.
The product, 177Lu-dotatate (Lutathera, Advanced Accelerator Applications), is a peptide receptor radionuclide therapy that is the first agent in its class. It was approved for the treatment of adult patients with somatostatin receptor–positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
These tumors can occur in any part of the gastrointestinal tract, including the pancreas, stomach, intestines, colon, and rectum. They affect about 1 in 27,000 people per year.
The primary treatment goal for patients with NETs is curative with surgery, as previously reported by Medscape Medical News. However, the majority of patients are diagnosed after the tumor has metastasized, so curative surgery often isn’t an option. Patients will then require postoperative medical management aimed at relieving symptoms and suppressing tumor growth and spread.
The usual first-line systemic treatment for GEP-NETs consists of a somatostatin analogue, either octreotide or lanreotide, explained Jonathan Strosberg, MD, associate professor and section head of the Neuroendocrine Tumor Program at Moffitt Cancer Center, Tampa, Florida. He was the principal investigator on the NETTER-1 trial that led to the new product approval.
Noting that 177Lu-dotatate has been approved for patients with progressive tumors that express somatostatin receptors, Dr Strosberg predicts that it will typically be given in the second-line setting and beyond, after progression occurs following treatment with a somatostatin analogue.
After progression, therapeutic options have been limited, he commented. “Everolimus is approved for patients with progressive disease, but even though response rates are low, rates of disease stability are high,” Dr Strosberg told Medscape Medical News.
“Sunitinib is approved for progressive pancreatic NETs only,” he explained, “And cytotoxic chemotherapy is also often prescribed for patients with pancreatic NETs, particularly for patients with aggressive disease.”
For patients with liver-dominant metastases, therapy includes hepatic arterial embolization along with other liver-directed treatments.
“There are no completed trials comparing Lutathera to any of the other therapies currently used, so the particular positioning of this treatment will depend on the judgment of the clinician,” Dr Strosberg commented.
“The responses associated with Lutathera compare very favorably with outcomes associated with other systemic therapies, although randomized clinical trials are clearly needed to compare treatments and help generate recommendations for sequencing of therapies,” he added.
Promising Phase 3 Results
The 177Lu-dotatate approval was based primarily on the phase 3 randomized NETTER 1 trial, which Dr Strosberg headed.
The results were published January 12, 2017, in the New England Journal of Medicine. They reaffirm interim data that were presented in 2015 and were described at the time as a “major advance.”
In this study, Dr Strosberg and colleagues randomly allocated 229 patients with well-differentiated, metastatic midgut NETs to receive either 177Lu-dotatate (n = 116 patients) with long-acting repeatable (LAR) octreotide at a dose of 60 mg alone (n = 113) every 4 weeks or a combination of 177Lu-dotatate at a dose of 7.4 gigabecquerels every 8 weeks (four intravenous infusions), plus best supportive care that included LAR octreotide at a dose of 30 mg.
The final results of the study showed that there was a clinically meaningful reduction in the risk for disease progression or death of almost 80% for patients receiving 177Lu-dotatate, as compared with patients receiving standard care.
The estimated progression-free survival (PFS) rate at month 20 was 65.2% with 177Lu-dotatate vs 10.8% in the control group, and the response rate was 18% vs 3% in favor of 177Lu-dotatate (P < .001).
Overall survival data are still immature. In the planned interim analysis of overall survival, 14 deaths occurred in the 177Lu-dotatate group vs 26 in the control group (P = .004).
Clinical data submitted for the product approval also included efficacy and safety data from an international, single-institution, single-arm, open-label trial conducted by Erasmus Medical Center in Rotterdam, the Netherlands. The trial included 1214 patients with somatostatin receptor–positive tumors, including GEP-NETs, who received 177Lu-dotatate as part of an expanded-access program.
In this cohort, complete or partial tumor shrinkage was reported in 16% of a subset of 360 patients with GEP-NETs who were evaluated for response by the US Food and Drug Administration.
Caution Needed For Week After Treatment
177Lu-dotatate belongs to a class of treatments called peptide receptor radionuclide therapy, which, according to the manufacturer, is a form of targeted treatment consisting of a targeting molecule that carries a radioactive component. The targeting molecule binds to a specific receptor on tumor cells. It is then internalized into those cells, and the radioactive component then destroys the tumor cells from within.
The agent consists of a radioisotope (177Lu) attached to a somatostatin analogue, explained Dr Strosberg. It is administered once every 8 weeks for four treatments and is typically administered by the nuclear medicine department.
Owing to the nature of the treatment, the patient becomes radioactive, he pointed out. “However, due to particle range and rapid decay, the risk to others is relatively low compared to most radiopharmaceuticals.”
However, caution is needed. “Patients are advised to sleep in separate beds that are at least 1 meter apart and to avoid contact with small children or pregnant women for a week after treatment,” Dr Strosberg said.
The cost of the treatment is as yet undetermined. Dr Strosberg expects that the cost of treatment will be covered by insurance.
Tidak ada komentar:
Posting Komentar