Professor Chen Yue’s team from the Department of Nuclear Medicine, Southwest Medical University Affiliated Hospital published prospective clinical research results
After neuroendocrine tumors (NENs) enter advanced stages, bone metastasis is one of the most difficult clinical problems. Bone-related events such as intractable bone pain, pathological fractures, and spinal cord compression not only seriously affect patients' quality of life, but are also clear adverse prognostic factors. Traditional peptide receptor radionuclide therapy (PRRT) can achieve systemic tumor control, but the depth of damage to bone metastases is insufficient; bone-targeted radionuclide alone can quickly relieve bone pain, but cannot cover a wide range of lesions such as primary lesions, lymph nodes, and liver metastases throughout the body.
Is there a solution that can combine the advantages of the two types of drugs into one?
Recently, Professor Chen Yue's team at the Affiliated Hospital of Southwest Medical University published the results of a prospective clinical study in the top journal of nuclear medicine, the European Journal of Nuclear Medicine and Molecular Imaging (EJNMMI). It was the first in the world to verify the safety and preliminary efficacy of 177Lu-DOTATATE combined with 177Lu-DOTA-IBA dual-targeted "nuclide cocktail" therapy in neuroendocrine tumor bone metastasis, providing an original Chinese solution to this long-standing clinical problem.
What is “nuclide cocktail” dual-targeted therapy?
When it comes to cocktails, everyone knows that they are mixing different drinks together. The nuclide cocktail therapy is to use two mature radioactive therapeutic drugs together and divide the work. It is not simply to double the dose of the drug.
177Lu-DOTATATE
Targeting the somatostatin receptor (SSTR) highly expressed on the surface of tumor cells, like a "biological missile", covers all SSTR-positive lesions throughout the body, including primary tumors, lymph node metastases, liver metastases and other lesions, to achieve systemic anti-tumor treatment.
177Lu-DOTA-IBA
Based on the high affinity of ibandronic acid to bone tissue, it specifically anchors the high bone metabolism area of bone metastases and continuously releases β-rays locally in the bone lesions. On the one hand, it inhibits osteoclasts and quickly relieves bone pain. On the other hand, it directly kills intraosseous tumor cells. It specializes in the "dead spots" of bone metastases that are difficult to cover with single-drug PRRT.
The two drugs are given to the patient one after another through infusion, and their targets do not conflict with each other, achieving a synergistic effect of 1+1>2. One treatment can simultaneously treat systemic tumors and bone metastases.
Four core advantages
Dual target complementation: filling the blind spot of single drug treatment
Treat tumors throughout the body: identify the unique SSTR receptors on the surface of neuroendocrine tumor cells and cover soft tissue lesions such as primary tumors, lymph nodes, and liver metastases;
Specializes in bone metastases: The drug will be precisely concentrated on the bone lesions to specifically remove cancer cells hiding in the bones.
From "individual combat" to "joint combat", one administration can complete the double attack on systemic tumors and bone metastases, leaving no blind spots in treatment.
Quick pain relief and long-lasting tumor control effect
After treatment, the overall bone pain relief rate was as high as 95.9%, of which 41.7% of patients had complete pain relief; most patients recovered from "requiring care by others" to "can perform normal daily activities"; there were no new bone-related events during the follow-up period, and the analgesic effect was stable and long-lasting.
Compared with traditional palliative radiotherapy, which can only cover local lesions, this program can act on all bone metastases throughout the body with one intravenous administration, providing more comprehensive and longer-lasting pain relief, eliminating the need to repeatedly go to the hospital for radiotherapy.
Under different evaluation criteria, the objective response rate (ORR) is 16.7%-50%, and the disease control rate (DCR) is 79.2%-87.5%.
After treatment, multiple indicators such as tumor volume, receptor expression level, and total bone metastasis volume were significantly reduced; the 12-month progression-free survival rate of the entire group of patients reached 75.3%, achieving the dual value of symptom relief and survival benefit.
Baseline 68Ga-DOTATATE PET/CT showed high SSTR expression in the pancreatic primary lesion (SUVmax 15.0), sternum (SUVmax 29.9), right hilar lymph node (SUVmax 12.0), right breast nodule (SUVmax 12.4), left pleura (SUVmax 13.6), and multiple bone lesions (B–E). After 3 cycles of dual-targeted radioligand treatment, the patient was reexamined 2 months later. The SSTR expression in the lesion was generally reduced, and the patient was evaluated as a partial response.
The curative effect is superimposed, but the toxicity is not superimposed.
Many people are worried: If two nuclide drugs are used together, will the side effects be doubled? Research has confirmed that this regimen is very safe, with no serious adverse drug reactions of grade 4 or above.
The radiation doses received by the kidneys, bone marrow, and liver, which are easily damaged by radiation, are within safe limits. The two drugs attack different targets. What increases is the radiation damage to tumor lesions. Normal body tissues will not bear more radiation. Together with conventional kidney protection methods, the overall treatment is safe and controllable.
Wide range of applications, a variety of patients can benefit
Neuroendocrine tumors are highly heterogeneous, and the biological behavior of tumors at different primary sites varies significantly. Subgroup analysis of this study confirmed that the benefits of the dual-targeting cocktail regimen are broad-spectrum:
·Tumor control and pain relief can be achieved regardless of gastroenteropancreatic origin (GEP-NENs) or non-gastroenteropancreatic origin (non-GEP-NENs) such as pheochromocytoma/paraganglioma;
·Patients with different bone metastasis loads and different pathological grades may also benefit from it.
China’s original plan opens a new paradigm of nuclide combined therapy
From single-target "individual combat" to dual-target "coordinated attack", this set of dual-targeted cocktail therapy directly addresses the pain points of NEN bone metastasis treatment. One treatment simultaneously achieves systemic anti-tumor and precise attack on bone metastases, taking into account disease control and bone pain relief, opening up a new treatment paradigm for advanced neuroendocrine tumor bone metastasis.
Different from the "zero to one" new drug research and development, this "mature drug mechanism complementation" combination strategy has a lower translation threshold and faster clinical implementation. It not only provides patients with better treatment options, but also provides replicable new ideas for the combination strategy of radionuclide targeted therapy.
From “drugs are available” to “better regimens”, from “monotherapy” to “combination optimization”, every breakthrough in nuclide therapy is striving for longer survival time and better quality of life for patients with advanced tumors. The Department of Nuclear Medicine of the Affiliated Hospital of Southwest Medical University will continue to delve into the field of integrated radionuclide diagnosis and treatment, based on clinical needs, focus on original breakthroughs, bring treatment hope to more patients, and help China's nuclear medicine diagnosis and treatment level steadily move towards the international forefront.
Source: Affiliated Hospital of Southwest Medical University