FDA Approves PRRT to Treat Neuroendocrine Tumors
source: pixabay.com

FDA Approves PRRT to Treat Neuroendocrine Tumors


Patients with inoperable or metastasized neuroendocrine tumors (NETs) may now benefit from recently FDA approved peptide receptor radionuclide therapy (PRRT) according to a recent article in MedPage Today. The approval has been a significant development for NETs patients.

PRRT treatments have been available since the 1990s in some Australian and European hospitals but not in the United States.

In 2018 the FDA approved Lu 177 DOTATATE (Lutathera) for the treatment of advanced NETs affecting the gastrointestinal tract or the pancreas.

Appropriate Enrollment

Patients with inoperable low or intermediate grade gastroenteropancreatic NETs with their disease progressing on standard therapy are the generally accepted candidates for these studies. This definition describes the majority of patients but excludes unusual subtypes and tumors considered to be high-grade.

However, there is ever-increasing data in support of using PRRT in higher-grade tumors and other subtypes.

About Phase III CASTOR TRIAL NCT0186074

The study highlighted the assessment of Lu 177 DOTATATE against interferon a-2b in patients diagnosed as having unresectable (inoperable) but progressive tumors that resist therapy in a climate of disease control.

The somatostatin receptor can be found on the surface of most mature NETs. The drug binds to this receptor. Once the radiopharmaceutical binds to the receptor, it becomes trapped in the cell. This allows the radiation to target the tumor cells.

About Phase III CASTOR Results

The encouraging results of the Phase III CASTOR trial included benefits relating to the quality of life, minimal toxicity, and meeting the trial endpoint of progression-free-survival.

Support for FDA Approval of PRRT

Approval for the Phase III CASTOR trial was obtained through the approval of two other trials.

The NETTER-1 trial involved two hundred twenty-nine patients with somatostatin tumors that were receptor-positive. Lutathera outperformed the current drug, octreotide, with a seventy-nine percent reduction in disease progression.

Evidence from the phase III NETTER-1 trial provided a significant increase in progression-free survival and overall survival benefits to NETs patients when treated with Lu 177 Dotatate versus treatment with octreotide.

The safety profile of Lu 177 Dotatate was favorable in general but more specifically for renal, hepatic, and hematological diseases.

The second trial that provided support for the FDA’s approval was a Dutch trial of 1,214 participants. The trial results showed an average of 29 months of progression-free survival. Secondary endpoints for these NETs patients after treatment with Lutathera were overall survival time of 63 months and an average of 36 months to progression.

PRRT’s Long-Term Efficacy

A 2019 twelve-year study reported in the Journal of Nuclear Medicine also supported the efficacy of PRRT’s management of NETs. The study analyzed PRRT relative to Lu 177 DOTATATE and Y 90 DOTATOC radiopharmaceuticals.

Seventeen women and twenty-seven men diagnosed with advanced tumors and expression of enhanced somatostatin receptor participated.

Overall survival averaged seventy-nine months. However, twelve years after the onset of the PRRT study, 32 percent of these patients (6 men and 8 women) remained alive.

Delivering the Therapy

Molecular Imaging is perhaps most commonly used to deliver the therapy. It is also the basis upon which the FDA and the EMA issued their approvals. Molecular Imaging includes four PRRT treatments with Lu 177 DOTATATE about two months apart.

This schedule may vary depending upon radionuclide, dosage, and the number of required treatments.

An amino acid solution is given to the patients that reduces radiation to the kidneys. This is mitigated with pre-medication to relieve nausea that is associated with the solution. In this regard, the majority of patients do not experience PRRT symptoms.

Fatigue is most commonly reported in the first few weeks of treatment. The majority of patients can be treated as outpatients.

There are, however, a series of complications that will require hospitalization such as a hormonal flare-up or damage related to NETs that affects end organs fed by the circulatory system.

The doctors find that patients with severe carcinoid heart disease present challenging treatment decisions. They caution that they do not treat patients who have low albumin levels or renal impairment.

In conclusion, the studies have demonstrated that there is a significant improvement in the quality of life and disease control after Lu 177 PRRT therapy.

What are your thoughts about the potential for PRRT’s effectiveness on inoperable tumors in the pancreas and GI tract?

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia four years ago. He was treated with a methylating agent While he was being treated with a hypomethylating agent, Rose researched investigational drugs being developed to treat relapsed/refractory AML.