Short PRRT Primer
What is Peptide Receptor Radionuclide Therapy (PRRT)?
For those who are still not sure what it’s all about. This is a non-surgical treatment which is normally administered intravenously. It’s based on the use of somatostatin receptors to attract a ‘radiopeptide’. The radiopeptide is a combination of a somatostatin analogue and a radioactive material. As we already know, somatostatin analogues (i.e. Lanreotide/Octreotide) are a NET cell targeting drug, so when combined with radioactivity, it binds with the NET cells and delivers a high dose of targeted radiation to the cancer while preserving healthy tissue. In general, patients tend to receive up to 4 sessions spaced apart by at least 2 months.
PRRT will not work on all NETs and not everyone will suited to this treatment. In general, for this treatment to be more successful, you must have somatostatin receptors in your tumors. Success rates are not 100% – it should not be considered a cure or ‘magic bullet’. However, the results are said to be pretty good. The NETTER-1 trial data which has led to formal approval in Europe, USA and other areas, can be found here.
LATEST ON EXPANDED NETTER-1 TRIAL DATA. “Novartis has announced presentation of a new analysis of Lutathera (lutetium Lu 177 dotatate) NETTER-1 data at the 2018 European Society for Medical Oncology (ESMO) congress examining the impact of Lutathera treatment on patients with low, medium or high liver tumor burden. The data show that Lutathera treatment results in significant improvement in progression free survival (PFS) regardless of the extent of baseline liver tumor burden (LTB), elevated alkaline phosphatase (ALP) liver enzyme or presence of large (>30mm diameter) lesion in patients with progressive midgut neuroendocrine tumors (NETs) compared to octreotide LAR alone.”
Read the latest news on the NETTER-2 trial here. This is designed to look at the benefits of using PRRT on Grade 2 and Grade 3 patients as a first line treatment.
Understanding the terminology is half the battle in understanding the latest developments. I’ve included Ga-68 PET scans within this section (or in more general terms Somatostatin Receptor PET (SSTR PET)) as the term ‘Theranostics‘ is becoming a commonly used theme. Theranostics is a joining of the words diagnostics and therapy.
LUTATHERA is the radionuclide ‘mix’ for use in Peptide Radio Therapy Treatment (PRRT). You may also see this drug called ‘Lutetium’ or ‘Lu-177 dotatate’, or just ‘Lu-177’ on its own. Yttrium 90 (Y-90) is a radionuclide also used in PRRT.
NETSPOT (USA) or SOMAKIT TOC (Europe) is not PRRT but it is the commercial names for the radiopeptide used in Gallium 68 (Ga-68) PET diagnostic scans.
Together they form a ‘theranostic pair’. Theranostics is apt as together (NETSPOT / SOMAKIT TOC and Lutathera), both target NETs expressing the same somatostatin receptor, with Lutathera intended to kill tumor cells by emitting a different kind of low-energy, short-range radiation than that of the diagnostic version.
Moreover, thanks to the theranostic approach that nuclear medicine allows, Novartis/AAA’s NETSPOT/SomaKit TOC products will be able to determine when Lutathera is the appropriate treatment.
Read more about Theranostics by clicking here.
Hasn’t the therapy has been in use for some time?
Of course, this therapy has been in use in Europe and some other places for some time but to be honest, they have been on a limited scale and never formally approved by national drug agencies. Despite its extensive use, the EU approval in 2017 was actually the very first approval of PRRT anywhere in the world. For example, in UK, it was used for some time for those in need but was removed from routine availability through a ‘slush fund’ formally known as the Cancer Drugs Fund – to cut a long story short, the funding source was cut off, although there are still ways of obtaining the treatment pending formal acceptance by the NHS (certain criteria apply).
In the meantime, I constantly see stories of patients travelling to Switzerland, Germany, Netherlands, Sweden, Great Britain and others; mostly at their own cost. However, it does indicate one thing, there is a huge unmet need in that many patients do not have access to the best treatments in their own country. I see this daily through many private messages.
What about Grade 3 (High Grade) Neoplasms?
The main treatment for Grade 3 is chemotherapy, particularly poorly differentiated. PRRT tends to work better with efficient somatostatin receptors (i.e. somatostatin receptor-positive tumors). The European approval wording only covers Grades 1 and 2. The US FDA approval indicates “somatostatin receptor-positive tumors”. It’s also worth noting that with Grade 3, working somatostatin receptors are more likely to exist in Grade 3 well differentiated NETs, particularly in the lower Ki-67 readings (less than 55%). However, there’s an interesting study from Australia which might be useful to read – check out the abstract here (note the full version is not available free).
2019 Updated data for Grade 3 Neuroendocrine Neoplasms:
“Compared to studies evaluating the efficacy of chemotherapy for NEN patients with a Ki-67 index less than or equal to 55 percent, PRRT has a longer overall survival rate–22 months versus 14 months,” the researchers pointed out. “These results suggest that PRRT, rather than chemotherapy, may be a superior first-line therapeutic option in selected patients with a high level of SSTR expression and a Ki-67 index of less than or equal to 55%.” Read more here.
Merkel Cell Carcinoma. Although not indicated for this type of Neuroendocrine Neoplasm, there is evidence to suggest that this skin Neuroendocrine Carcinoma does express somatostatin receptors. Read more here.
What about Pheochromoctyoma/Paraganglioma?
This article discusses the efficacy of PRRT in Pheo/para – click here. There’s actually still a trial for Pheochromocytoma/Paraganglioma (Pheo/Para). It is known that Pheo/Para can have somatostatin receptor tumors so a useful trial. The aim of the trial is to assess the safety and tolerability. You can read about the trial here.
Where can I get PRRT?
The aim of this section is to update on a regional basis in order to inform an international community of followers and readers.
I wanted a place to review what is happening globally given my following. In many countries, however, I’m dependent on feedback from patients in those countries. Please note this is not intended to be a 100% complete breakdown on everything about PRRT or PRRT centres – it’s a summary. It should be clear from below but please bear that in mind when reading.
This section of this article will cover each region, indicating where PRRT can be obtained (as far as I know). It is not designed to indicate whether this is through public or private facilities (this will depend to too many factors beyond the reach of this article). Please note this is not intended to be a 100% complete breakdown on every single PRRT centre – it’s a summary. This actually should be clear from below but please bear that in mind when reading.
On 29 August 2018. National Institute for Health Care Excellence (NICE) England has formally published that Lutetium (177Lu) oxodotreotide, within its marketing authorisation, is an option for treating unresectable or metastatic, progressive, well-differentiated (grade 1 or grade 2), somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumours (NETs) in adults. CLICK HERE to read the approval. Currently available in the following NHS locations:
- London – at least 2 locations – Royal Free, Guys and St Thomas
- Liverpool – The Royal
- Manchester – The Christie
- Sheffield – Weston Park
- Bristol – Bristol Oncology Centre
- Newcastle – Freeman Hospital
- Coventry – University Hospital
Anecdotal mention of Leicester but waiting to hear confirmation.
On 9 July 2018. The Scottish Medicines Consortium (NICE equivalent) has approved lutetium 177Lu (Lutathera) for patients in NHS Scotland. Good news for Scotland once their hospitals have the capability to deliver. Scottish patients would then not need to travel to England for the NHS Scotland funded treatment. Read more here.
It is funded in Wales and Northern Ireland but is currently administered in England with inter NHS budget transfers.
On 7th Feb 2019, Health Canada approved Lutathera™ (lutetium (177Lu) oxodotreotide) for the treatment of unresectable (not removable by surgery) or metastatic, well-differentiated, somatostatin receptor-positive (expressing the somatostatin receptor) gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in adults with progressive disease. The treatment was previously available on a trial basis. Read more here.
Site update to follow but the following trial locations may be up and running first:
- Juravinski Hamilton
- LHSC London
- PMCC Toronto
- Sunnybrooke Toronto
- Cross Cancer Institute, Edmonton
PRRT was approved in USA on 26 Jan 2018. The approval is for the treatment of somatostatin receptor positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs), including foregut, midgut, and hindgut neuroendocrine tumors in adults. CLICK HERE.
The extended access program (trial) is no longer offered but these locations should be ahead of the game in terms of provision, notwithstanding insurance and provision of sufficient nuclear material.
In the meantime, known USA sites offering routine “live site” insurance based PRRT treatment are as follows – please note information has been gleaned from US patients due to no other consolidated source of this information being readily available. It’s possible some patients got mixed up between trial locations and live locations so let me know of any omissions or additions/corrections – thanks in advance.
DRAFT – NOT YET COMPLETE – (as at 16 May 2019)
|STATE||LOCATION||Due in Service?||CONTACT DETAILS|
|Arizona||Banner||Now||Dr Boris Naraev|
|California||UCSF Medical Center Mission Bay San Francisco||Now||tbc|
|California – Antioch||Kaiser Permanente Antioch Medical Center||Now||tbc|
|California||Cedars Sinai Medical Center LA||now||tbc|
|California||Stanford Medical Center||Now||tbc|
|California||Kaiser Permanente Los Angeles Medical Center||Now||tbc|
|California||Hoag Hospital Newport Beach||Now||tbc|
|California||Kaiser Santa Clara Medical Center||Now||tbc|
|California||City of Hope LA||Now||tbc|
|Connecticut||Yale New Haven Medical Center||Now||tbc|
|Connecticut||Hartford Hospital||Now||Salner, Andrew, MD
|Colorado||Rocky Mountain Cancer Center Denver||Now||Dr Eric Liu|
|Colorado||University of Colorado UC Health Denver||Now||tbc|
|Florida||Moffat Tampa||Now||Dr Strosberg|
|Florida||University of Miami||Now||tbc|
|Florida||Winter Park, Florida Radiation Oncology Orlando||Now||David Diamond MD|
|Georgia||CCTA Newnan, Atlanta||Now||Dr. Phan|
|Hawaii||Queen’s Medical Center||Now||Dr. Marc Coel|
|Idaho||Mountain States Tumor Institute at St. Luke’s Hospital, Boise||Now|
|Idaho||Eastern Idaho Regional Medical Center, Idaho Falls, Idaho||Now|
|Illinois||Rush University Chicago||Now|
|Illinois||The University of Chicago Medicine||now||Xavier M. Keutgen, MD|
|Illinois||Loyola University Medical Center Maywood||now||tbc|
|Indiana||Indiana University Health||now||tbc|
|Iowa||University of Iowa||now||Dr T O’Dorisio|
|Kansas||University of Kansas Medical Center Fairway||now||tbc|
|Kentucky||University of Kentucky, Markey Cancer Center||now||tbc|
|Maryland||John Hopkins Baltimore||now||tbc|
|Massachusetts||Dana Farber Boston||Now||tbc|
|Massachusetts||Massachusetts General Hospital||Now||tbc|
|Michigan||Detroit – Karmanos Cancer Center||Now||tbc|
|Minnesota||Mayo Rochester||Now||Dr. Thor Halfdanarson|
|Minnesota||University of Minnesota Health||Now||tbc|
|Missouri||Sara Canon Cancer Center Kansas City||Now||tbc|
|Missouri||Siteman Cancer Center St. Louis/Barnes Jewish Hospital St. Louis||Now||tbc|
|Nebraska||CHI Bergan||Now||Dr Samuel Mehr|
|Nebraska||Nebraska Cancer Specialists Omaha||Now||Dr Samuel Mehr|
|New York||Lenox Hill NYC||Now||tbc|
|New York||Sloan Kettering||Now||tbc|
|New York||Stony Brook University Cancer Center Long Island||Now||Nurse Navigator, Patty Zirpoli, RN|
|New York||Roswell Park Buffalo||Now||Dr Iyer|
|New York||Mount Sinai||Now||tbc|
|New York||NYU Langone||Now||tbc|
|North Carolina||Dukes Durham||Now||tbc|
|Ohio||The James, Columbus||Now||Dr Shah|
|Oregon||Oregon Health & Science University (OHSU)||Now||tbc|
|Pennsylvania||Fox Chase Philadelphia||Now||Dr Paul Engstrom|
|Rhode Island||Rhode Island Hospital Providence||Now||Dr Paul Engstrom|
|South Dakota||Sanford in Sioux Falls||now||tbc|
|Texas||MD Anderson Houston||Now||tbc|
|Texas||Excel Diagnostics Houston||Now||tbc|
|Texas||CHI St Lukes Houston||Now||tbc|
|Texas||BAMC San Antonio(VA) Houston||Now||tbc|
|Utah||Huntsman Cancer Institute, Salt Lake City||Now||tbc|
|Vermont||University of Vermont Medical Center||Now||Jay Kikut, MD, Director of Nuclear Medicine and PET|
|Virginia||Carilion Clinic Roanoke||Now||tbc|
|Washington (State)||Virginia Mason Seattle||Now||Dr. Hagen Kennecke|
|Washington (DC)||VMedStar Georgetown University Hospital||Now||tbc|
|West Virginia||VMU Cancer Institute Morgantown||Now||Shalu Pahuja, M.D|
|Wisconsin||UW Health Madison, Carbone Cancer Center||Now||Noelle K. LoConte, MD Specialty: Medical Oncology Primary Location: UW Carbone Cancer Center (608) 265-1700 (800) 323-8942|
|Wisconsin||Froedtert Milwaukee||Now||Dr Thomas|
Europe (excluding UK which is listed above)
The European Medicines Agency (EMA) “market authorisation” received a positive indication on 20th July followed by EC approval on 29 Sep 2017. The positive indication reads “Lutathera is indicated for the treatment of unresectable or metastatic, progressive, well differentiated (G1 and G2), somatostatin receptor positive gastroenteropancreatic neuroendocrine tumours (GEP NETs) in adults”. Of Course, the decision to fund the drug will be with national approval organisations. Whilst I’m sure there are many more, these well-known centres have been making PRRT available for some years (but please note there are others):
Finland – Helsinki: Docrates Cancer Center
– Zentralklinik Bade Berka – click here
– Berlin, Klinik für Nuklearmedizin
Italy – Milan, European Institute of Oncology
Netherlands – the combined NET centres of the UMCU Utrecht and AVL Amsterdam have an ENET certification and they both do PRRT.
UMCU – Utrecht
(only available in dutch)
AVL – Amsterdam
(only available in dutch)
Poland – Poland, Maria Skłodowska-Curie Institute of Oncology, regional branch in Gliwice
Serbia – Clinical Center Kragujevac, Centre of Nuclear Medicine
Slovenia – Ljubljana, University medical Centre Ljubljana
Sweden – Department of Endocrine Oncology Uppsala University Hospital – click here
Switzerland – University Hospital Basel, Radiology & Nuclear Medicine Clinic – click here
I’d be interested to hear from countries in Europe with their full list of centres or a link to it.
Australia seems to be ahead of the game or that is what I sense when I read output from there. There’s a good section on the Australian effort – click here.
These guys have had to fight to get some progress on the provision of PRRT. Currently New Zealanders have to go to Melbourne Australia for treatment – almost 50 New Zealanders with NETs are currently raising tens of thousands of dollars to pay for treatment in Australia because the life-prolonging treatment isn’t available locally. But this could change in 2018. Unicorn Foundation New Zealand announced that Pharmac, the New Zealand government agency that decides which pharmaceuticals, have said that PRRT will be funded for patients with medium priority for the treatment of unresectable or metastatic, well-differentiated NETs (irrespective of primary site) that express somatostatin receptors.
- Pretoria – Steve Biko Academic Hospital and the University of Pretoria
- Johannesburg – The Wits Donald Gordon Hospital
- Durban – Umhlanga Molecular Imaging and Therapy Centre of Excellence at Umhlanga Hospital
- Cape Town – Tygerberg Hospital
Middle East, Asia and the Far East
Turkey – Istanbul, Dr.Levent Kabasakal.
Lebanon – The American Hospital of Beirut – Dr Ali Shamseddine “We have started using Lu-177 here in Lebanon. So far, we have treated 3 patients, with good response. The operational cost is much less than in Europe”.
|Ali Shamseddine, MD, CHB||Professor and Head of Divisionfirstname.lastname@example.org|
India – Mahatma Gandhi Cancer Hospital, Visakhapatnam. Recently started radionuclide therapy. Although only currently available privately, some patients have been sponsored by the companies that they work for. Point of contact is Dr. K. Raghava Kashyap. I’ve been assured by CNETS India that many locations have PRRT capability – contact them direct please. Also – TATA Memorial Hospital Mumbai (waiting time is long, but cost is low: $200) and there are private clinics in Pune (cost is $1500) and Bengaluru (cost is around $6000). (Info from Russian patient group).
Pakistan – check out this article – click here
Philippines – St. Luke’s Medical Center, Global City, Taguig, Metro Manila.
What’s next for NETs PRRT?
- two radiopeptides together;
- radiopeptides in conjunction with other chemotherapies (check out my article PRCRT);
- repeated administrations of the radiotherapies;
- other radionuclide-peptide combinations.
- increasing the number of indications for this therapy, including other disease targets;
- e.g. they are already using it for Prostate Cancer.
- e.g. new radionuclides – see my article about the COMPETE trial.
- See article “PRRT – The Sequel? – Targeted Alpha-emitter Therapy (TAT)”
- The next generation? 177Lu Ops 201 (Satoreotide)
See this great summary from NET Research Foundation of what might be next plus basic facts about PRRT – click here
Thanks for reading