Lessons learned as a radioligand therapy patient

3 August 2021

In 2007, I heard the words that nearly 40% of people in the US will hear in their lifetime: “You have cancer.”

My type of cancer, neuroendocrine tumors or NETs, are considered rare and at the time had few approved treatments available. Like most people, after receiving a diagnosis and listening to my doctors, I spent time on the internet trying to find information that could help me better understand my disease, looking for possible treatments and networking with other people who were dealing with the same challenges that I was facing.

This is something that my local patient support group, Northern California CarciNET Community, encourages all patients and caregivers to do: educate themselves about neuroendocrine tumors and treatments by networking with other patients. One way of doing this is attending patient education conferences, where medical experts explain the latest thinking on treatments and care.

This is how, in the fall of 2008, I found myself in Toronto, Canada, listening to a lecture by Prof. Dr. Richard Baum from Germany discussing radioligand therapy imaging and the advances that were being made to treat neuroendocrine tumors. Six weeks after the conference, I arrived in Germany to undergo a new type of targeted imaging using Gallium-68 DOTATOC. Six months later, the results of that imaging procedure were used to guide my next course of treatment, which would use the same targeting agent (or ligand) but with a therapeutic isotope of yttrium-90, which was intended to stabilize or reduce the size of my neuroendocrine tumors. Over the course of the next eight months, I had several more cycles of radioligand therapy, which stabilized my diseases for more than six years.

Why was radioligand therapy hard to access in the US?

At the time I did not question why radioligand therapy was available in Germany and not in the US. Despite encouraging results being announced for NETs, many patients and providers were discouraged by the therapy’s lack of availability in the US.

Targeted radioisotope therapies are not new. 2021 marks the 80th anniversary of the radioiodine therapy first performed by Dr. Saul Hertz, and more than 25 years since the first studies of radioligand therapy performed in NETs patients in the Netherlands. So why was radioligand therapy not widely available in the US in 2009?

Explanations from patient groups and medical conferences varied widely, but usually focused on a couple of reasons: that regulators in one country were holding up an approval, or that the practice of medicine was more advanced in one country over another. Many patients in the US contacted their elected representative to insist that the Food and Drug Administration (FDA) approve radioligand therapy, so that they wouldn’t have to travel to Europe for treatment.

What the majority of patients and US providers did not realize was that the use of radioligand therapy for NETs did not get approved in Europe until 2017 (just six months before the US). Until then, the treatment was not widely available in Europe either, just at select centers that could perform it by providing it as compassionate care. Patients were blaming regulators for not approving the therapy, but the regulators had not been approached by manufacturers and therefore had nothing to approve (or deny).

Why didn’t regulators have something to approve? There are many potential explanations, but put simply there was not a single pathway or framework for getting this work done. Centers that could offer the treatment under their country’s regulation were not in the position to apply for registration.  Manufacturers needed to be convinced that the market for the therapy would be large enough to support the cost of the trials and the supply chain logistics required for registration. They also needed to have enough data to show that benefits of the treatment outweigh the risk and offer significant benefits over alternative treatments, if available.

In 2015, a large-scale phase 3 trial (NETTER-1) was completed, which resulted in the approval of lutetium-177 DOTATATE, a form of radioligand therapy, in Europe in 2017 and the US in early 2018. Soon thereafter, another radioligand therapy was approved in the US for rare kinds of tumor (pheochromocytoma and paraganglioma).

Tackling myths and misinformation

While the approval of new radioligand therapies has changed the treatment paradigm for people with NETs, and pheochromocytoma and paraganglioma, there are still many misconceptions. High on the list is the belief that all radioligand therapies and other targeted radioisotope therapies are alike, and that patient information materials that were previously used for radioiodine therapy can be reused with other forms of radioligand therapy.

Each radioligand therapy needs its own set of patient information and release instructions specific to the ligand and isotope being used. The release instructions for lutetium-177 DOTATATE should be different than that of radioiodine, and while lutetium-177 PSMA and lutetium-177 DOTATATE use the same isotopes, the instructions for each should be specific to the cancer being treated.

A great deal has been learned about overcoming the misconceptions and challenges in the process of getting radioligand therapy approved. Much of this learning has been incorporated into the Radioligand Therapy Readiness Assessment Framework to help manufacturers, medical societies, providers, regulators and patients better understand the complexity of delivering new radioligand therapies in their countries, so that other patients will not have to endure another 20+ years between inpatient trials and an approved radioligand therapy.

Myths and misinformation become ingrained over time, and lack of credible information allows them to propagate. We therefore need to be ready to quickly, and sustainably, integrate new therapies into clinical practice.

Josh Mailman, President, NorCal CarciNET Community US



Josh Mailman, President, NorCal CarciNET Community US