A step forward in the advancement of precision cancer treatments, theranostics combines diagnostic imaging and molecular radiotherapy to target and kill tumor cells, while preserving healthy ones. Theranostics was first used to treat thyroid disease decades ago. Thanks to the development of new radiopharmaceuticals and ongoing research, it has now become a viable treatment option for patients with select neuroendocrine tumors and is also showing promise in the treatment of metastatic prostate cancer.
A New Way to Manage Neuroendocrine Tumors
Patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are traditionally treated with the chemotherapy drugs octreotide or lanreotide. “With neuroendocrine cancers in general, the treatment, planning and care is more of a marathon than a sprint,” says UVA Cancer Center oncologist Matthew Reilley, MD. “Typically, we’re thinking long-term care, over years. A lot of patients are asymptomatic and the cancer is picked up incidentally. The goal of treatment is to maintain the disease as effectively as possible before patients develop problems or complications.”
When these drugs no longer inhibit tumor growth, patients have historically had few options. But today, leading medical centers with established nuclear medicine programs like UVA Health are offering one of the theranostic platforms as a second-line treatment for select patients with GEP-NETs. More specifically, they are offering Lutathera ® (lutetium 177 Dotatate), the first U.S. Food and Drug Administration-approved peptide receptor radionuclide therapy (PRRT).
Hitting the Target
Lutathera is indicated for patients with a specific tumor type. That is, progressive GEP-NETs with the somatostatin receptor (SSTR2), a protein found on the membrane of the tumor cell.
To identify SSTR2, the patient is injected with the radionuclide imaging agent Ga-68 DOTATOC, which was designed to bind to SSTR2, causing it to light up on a PET scan. Once the expression of SSTR2 is confirmed by PET imaging, the radionuclide lutetium-177 Dotatate can subsequently be used to target and kill these tumor cells. Healthy cells without these proteins are not affected by the drug.
“We look at how densely these receptors are expressed in the tumor to determine: Is the individual patient a good candidate for PRRT? Will they benefit from this targeted treatment? That’s the first step,” says Lale Kostakoglu-Shields, MD, MPH, Director of the UVA Division of Nuclear Medicine and Molecular Imaging.
Eligible patients with SSTR2-positive tumors receive four cycles of radiation with two months in between each cycle, totaling an eight-month course of treatment. “This treatment is different because it’s an infusion, so it’s internally delivered radiation rather than externally given,” says Reilley. “It’s a great way of delivering a targeted payload of radiation directly to the tumor cells themselves.”
Progress Leads to Promise for Expanded Use
At UVA Cancer Center, Lutathera has been provided through the peptide receptor radionuclide treatment program, a collaborative effort of the Division of Nuclear Medicine and Hematology & Oncology, since March 2020. Because this is an eight-month treatment regimen, it’s still too soon to assess the patients’ response to treatment, says Kostakoglu-Shields.
However, results from the study that led to the FDA approval of Lutathera, the Netter-1 phase 3 clinical trial, showed a 79% reduction in the risk of disease progression and death in patients on Lutathera as compared with high-dose, long-acting octreotide (60 mg). And the overall response rate in patients on Lutathera was three times greater than those patients on high-dose octreotide alone.
Anecdotally, Kostakoglu-Shields and Reilley are seeing similarly positive results. “So far, we’ve seen patients with good disease control and some have shown tumor shrinkage that wasn’t occurring with prior treatments,” says Reilley.
Because of these promising outcomes, UVA Cancer Center researchers are already looking for additional uses for Lutathera. “We are now focused on evaluating clinical trials and reviewing patients to determine if we can provide more options to those with other tumor types and combination therapies for neuroendocrine patients,” says Reilley.
Kostakoglu-Shields and Reilley attribute the launch and success of the UVA PRRT program thus far to their multidisciplinary, collaborative approach to care. “This is a very delicate and detailed program,” says Kostakoglu-Shields. “It’s not just nuclear medicine and oncology. We have a big team working with us — nurses, technologists, physicians, pharmacists and coordinators. You need to have all the pieces come together and everyone must understand the importance of their role for a successful operation. We have established that collaborative framework here at UVA; everyone is conscientious and achieves high performance, so we are very efficient at every step of execution. We also include referring providers in all communications, so they are well connected and can give better patient care”
Theranostics Will Be Part of the Future of Prostate Cancer Treatment
The theranostics approach is also now an option for men with metastatic, castration-resistant prostate cancer. One of these treatments utilizes the radiopharmaceutical called Xofigo (Radium 223), which was designed to target metastatic sites in the bones. “We have a good number of patients we are treating currently with this agent,” says Kostakoglu-Shields.
Another theranostic platform in clinical trials now involves the use of radiolabeled prostate specific membrane antigen (PSMA) to image and treat metastatic, castrate-resistant prostate cancer. To identify PSMA-positive cells on a PSMA PET-CT scan, nuclear medicine physicians use the recently FDA-approved radioactive tracer Ga 68 PSMA or F18 PSMA.
“PSMA PET imaging provides a very high sensitivity to detect small deposits of tumors that are otherwise undetectable,” explains Kostakoglu-Shields. “Oncologists and radiation oncologists are looking forward to using this targeted imaging test to design their treatment approach, adjust their treatment fields, as well as monitor to determine response.”
“If patients are positive for PSMA expression on the PET/CT scan, then they are eligible to receive the targeted Lu-177 PSMA treatment,” says Kostakoglu-Shields. In the near future, she predicts this PSMA-targeted approach will be incorporated more broadly into prostate cancer treatment.
“Prostate-targeted imaging and therapy will transition into clinical practice very soon, identifying those patients who have biochemical recurrence of disease, but present with undetectable tumors utilizing currently available imaging techniques,” she says. “All of these developments are very exciting and innovative in the quest of overcoming cancer progression and making it a chronic disease rather than a fatal one. Overall, at UVA, it is our main agenda to help move toward personalized medicine.”
Sign Up for a Virtual Information Session
Dr. Kostakoglu and Dr. Reilley are hosting a 20-minute virtual information session about NETs and Lutathera on Thursday, September 23 at noon. You’ll get the chance to meet them and discuss how they partner with you to provide exceptional care to your patients. Register to get more information.
Have a question about Lutathera or want to schedule a patient? Call our Lutathera scheduler at 434.924.9333, opt. 4, or the Lutathera nursing line at 434.982.5240.