At Nucleus RadioPharma, there’s nothing we enjoy more than educating our community on the latest advancements in radiopharmaceuticals, which is why we recently hosted two live events with top experts in the field.
While many tuned in for our two most recent events, “What Does Novartis’s Pursuit of a Label Expansion for Pluvicto Possibly Mean for Patients and the Field of Radiopharmaceutical Therapy?” featuring Dr. Geoff Johnson and “What Should Providers and Patients Know About Radiopharmaceutical Clinical Trials?” featuring Dr. Oliver Sartor, we’ve summarized the key insights below for those who either missed them or want to revisit the information.
“What does Novartis’s pursuit of a label expansion for Pluvicto possibly mean for patients and the field of radiopharmaceutical therapy?”
Novartis’s pursuit of a label expansion for Pluvicto (Lutetium-177 PSMA-617) marks a shift in radiopharmaceutical therapy as it broadens its reach to patients who have not undergone chemotherapy.
Traditionally, Pluvicto has been administered to patients at the end of their cancer journey after they’ve exhausted other options, including chemotherapy. But this label expansion, pending FDA review of the PSMA-4 trial data, could increase access and redefine treatment pathways. For the many patients who either cannot tolerate chemotherapy or wish to avoid its harsh side effects, Pluvicto would offer an attractive alternative.
Radioligand therapy (RLT) before chemotherapy is an exciting possibility, especially as recent trials keep showing promising results in patients pre-chemo. Trials like PSMA-4 are breaking new ground with crossover designs—allowing patients who start in the control group to switch over to RLT if their cancer progresses. However, while crossover designs have been great for patient participation, they also present challenges in analyzing the data, particularly for overall survival rates. With up to 80% of patients crossing over, many on both arms of the study end up receiving the therapy, which complicates direct comparisons.
Still, these insights are shaping the way we design new trials, highlighting the importance of patient-centered options like crossover while also ensuring that data remains meaningful. If these trials keep showing strong results, RLT could emerge as a standard treatment before chemotherapy. As Dr. Geoff Johnson pointed out, unlike chemotherapy, providers can administer RLT in cycles over time for those who respond well and offer a way to manage cancer progression with fewer side effects.
Currently, patients have options when discussing treatment for metastatic castrate-resistant prostate cancer (mCRPC) with their providers. They can receive androgen signaling inhibitors (ARSI) treatments such as abiraterone and enzalutamide or chemotherapy like docetaxel and cabazitaxel. Other options include non-targeted radiotherapy, radium-223 dichloride for bone-only metastasis, and PARP inhibitors olaparib, rucaparib, niraparib, or talazoparib if you have specific HRR-positive genetic mutations. For some patients, you can receive the PARP inhibitor combined with the androgen-targeted agents.
The potential to integrate RLT into earlier-stage therapies also opens new treatment options. Currently, for the targeted radiopharmaceutical (RLT), lutetium Lu 177 vipivotide tetraxetan (PLUVICTO®), you must have received treatment with one ARSI and chemotherapy. With trials such as PSMAfore, SPLASH, and ECLIPSE, the targeted RLT was studied in mCRPC before a patient received chemotherapy. All three of these trials have reported positive primary endpoints, but none have been submitted for FDA approval at this time.
But as radiopharmaceuticals continue to advance, so do the logistical hurdles. Radioligand therapies rely on isotopes with very short half-lives—like Lutetium-177, which loses half of its potency every six days. Because manufacturing often spans a vast distance (sometimes over multiple countries), and each step has strict timelines, there’s a tight race to get these therapies to patients on time.
With demand on the rise, especially as indications expand, the infrastructure supporting these therapies has to grow in step. While large academic centers are ramping up capacity, smaller hospitals may struggle to keep pace, revealing a clear need for broader manufacturing and distribution networks to make these treatments more accessible to patients everywhere.
Reimbursement policies also play a crucial role. Currently, Medicare’s reimbursement model includes a three-year pass-through period for diagnostic radiopharmaceuticals like Gallium-68 PSMA-11 and F-18 PSMA DCFPyL. After this period, hospitals are reimbursed only a fraction of the cost, making the scans financially unsustainable for many institutions.
The FIND Act aims to address these challenges and proposes reimbursement adjustments to maintain access to diagnostic agents essential for identifying eligible patients for RLT. The Centers for Medicare & Medicaid Services (CMS) recently released a proposed rule aligned with the FIND Act, which, if adopted, could help ensure these diagnostics remain accessible, especially in community hospitals with tighter budgets.
“What should providers and patients know about radiopharmaceutical clinical trials?”
Radiopharmaceutical clinical trials are bringing a unique approach that blends diagnosis and therapeutic uses of radioisotopes into one process—what’s known as theranostics. Theranostics radiopharmaceuticals can both “see” and “treat” cancer. By tagging a molecule with a diagnostic isotope detectable by PET or SPECT imaging, providers can visualize the exact location of cancer. Then, with a therapeutic isotope, they can precisely target and treat those same cancerous areas. It’s a powerful new way of managing cancer.
In practice, diagnostic imaging is often the first step before initiating a full therapeutic phase. Imaging trials are typically faster, more cost-effective, and provide early insights into a molecule’s binding capabilities. Prostate cancer, for example, has become a focal point due to the discovery of prostate-specific membrane antigen (PSMA), which is highly expressed in prostate cancer cells and can be targeted by diagnostic and therapeutic agents. PSMA-targeted therapeutics, such as Lutetium-177 PSMA-617, have proven effective, marking a milestone for radiopharmaceuticals and signaling a bright future for this targeted approach.
The approach used in prostate cancer is a model researchers hope to replicate in other cancers. Neuroendocrine tumors, which express the SSTR2 receptor, have also responded well to theranostic treatments. However, extending this approach to more common cancers—like breast, lung, and colon—requires discovering new targets and developing corresponding ligands that selectively bind to them.
Not all cancers express easily identifiable targets like PSMA, making target discovery a central focus for researchers aiming to expand theranostics. These cancers may require innovative approaches, such as developing ligands that adapt to diverse tumor microenvironments.
For providers, keeping up with advancements in radiopharmaceuticals can be challenging, especially since most trials are conducted in major centers equipped with specialized technology. Staying current with FDA approvals and landmark trial outcomes is essential to understanding which treatments are yielding results and when referral to a center conducting radiopharma trials might benefit a patient. While it may be unrealistic for every provider to specialize in this rapidly evolving field, resources like The New England Journal of Medicine and FDA updates are valuable for staying informed.
Radiopharmaceuticals also enter an increasingly diverse oncology toolkit that includes options like antibody-drug conjugates (ADCs), CAR-T cells, and bispecific antibodies. Each approach has its strengths and limitations: CAR-T cells, for instance, show promise in hematologic cancers but have yet to demonstrate consistent efficacy in solid tumors.
Radiopharmaceuticals, by contrast, allow for predictable, focused targeting when the appropriate ligand and isotope are identified. Providers must have a deep understanding of each modality’s benefits and challenges, especially when guiding patients toward suitable trials or treatments.
Another important consideration for providers is accessibility. While it’s true that radiopharmaceutical trials are largely held in academic centers, the ultimate goal of these trials is to benefit patients everywhere.
As these trials advance, new knowledge and treatment options can diffuse into community settings, allowing providers across various healthcare settings to access these tools. Providers in regional or community settings may still benefit from trial outcomes even if they’re not directly involved in the trials. As more data from these trials is shared and as regulatory approvals grow, the reach of radiopharmaceuticals will expand and help providers in diverse settings offer their patients access to targeted care.
What’s in store for radiopharmaceuticals in 2025?
Watch the recording of our December 11th, 2024 webinar: “Greatest Hits in Radioligand Therapy: A Year in Review and Prognostications for 2025,” where we reflected on pivotal moments from 2024 and offered a look at advancements on the horizon of the upcoming year.