There’s a lot of questions doing the rounds on forums and messages about the approval of Lutathera (PRRT) in USA, Europe and other places. This is not a place just for one particular country, I want a place to review what is happening globally given my following. In many countries, however, I’m dependant on feedback from patients in those countries.
Short PRRT Primer
For those who are still not sure what it’s all about. This is a non-surgical treatment and is based on the use of somatostatin receptors to attract a ‘radiopeptide’. It is normally administered intravenously. The radiopeptide is a combination of a somatostatin analogue and a radioactive material (radionuclide). As we already know, somatostatin analogues are a NET cell targeting protein, so when combined with the radionuclide, it binds with the NET cells and delivers a high dose of targeted radiation to the cancer while preserving healthy tissue. Simple!
PRRT will not work on all NETs and not everyone will suited to this treatment. For this treatment to be successful, you must have somatostatin receptors in your tumors. Success rates are not 100%.
The results from the NETTER-1 trial which has led to formal approval in Europe and USA can be found here.
Understanding the terminology is half the battle in understanding the latest radionuclide developments. I’ve included Ga-68 PET scans as the term ‘Theranostics‘ is becoming a commonly used theme.
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 is not PRRT but is the radionuclide mix for use in Gallium 68 (Ga-68) PET diagnostic scans and was recently approved in USA. SOMAKIT TOC is essentially the European equivalent of NETSPOT and is approved in Europe.
Together they form a ‘theranostic pair’. Theranostics is a joining of the words diagnostics and therapy. 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, AAA’s NETSPOT/SomaKit TOC products will be able to determine when Lutathera is the appropriate treatment.
LATEST HEADLINE – Next approval due – UK.
Latest news from UK. 20 Feb 2018. NICE confirm PRRT will be included in the technology appraisal committee meeting on 11 April 2018. They don’t expect to publish the outcome until 25th July 2018 at the latest. CLICK HERE
Timeline of interest in the UK decision
ALL – 7 Dec 2017. Novartis and Advanced Accelerator Applications (AAA) Announced that Novartis is buying AAA and the process has been completed. AAA is now a Novartis Company. Read here This will not have any effect on approval timelines.
EUROPE – 29 Sep 2017. AAA Announced that the European Commission (EC) has approved the use of Lutetium Lu 177 Dotatate (Lutathera®). Despite the treatment being used for over 10 years, this is apparently the first ever approval of the therapy. EU constituent countries are now free to fund and implement services. In the UK, now awaiting action by NICE (see announcement below 3rd and 11th Aug). Read here
UK – 11 Aug 2017. AAA responds to UK drug appraiser National Institute for Health and Care Excellence (NICE) negative recommendation. Read here
UK – 3 Aug 2017. Currently, NICE (the UK equivalent of FDA) are not recommending Lu-177 Lutathera based on cost. This is only a draft recommendation and another announcement is expected end Sep 2017. More to follow when known. This is a blow for patients in England. Read here
UK – 2015. PRRT was removed from the Cancer Drugs Fund by NHS England
The situation is confusing – 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 as 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.
The next 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).
The aim of this section is to update on a regional basis in order to inform an international community of followers and readers.
Europe (EU associated countries)
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, well-known centres have been making PRRT available for some years:
Netherlands – Rotterdam Treatment Centre – click here
Sweden – Department of Endocrine Oncology Uppsala University Hospital – click here
Switzerland – University Hospital Basel, Radiology & Nuclear Medicine Clinic – click here
Germany – Zentralklinik Bade Berka – click here
UK – Royal Free Hospital – click here
I’d be interested to hear from other countries in Europe with their list of centres.
In UK, despite the EC approval on 29 Sep 2017, NICE (drug approvals agency) are currently not recommending PRRT (Lu-177) due to what looks to me like cost grounds. One theory is that this is a metaphor for price negotiation between NHS and AAA. This is a particularly controversial issue for UK as the drug was removed from routine use (Cancer Drugs Fund) in 2015. Why wait in UK? There are ways to get access to PRRT via different funding sources. Ask your specialist because this possibility is unfortunately not very well publicised. PRRT is funded in Scotland, Wales and Northern Ireland. The NICE approvals process only covers England. See headline update above.
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 – (full guidance will be updated when received)
The extended access program is on hold but these locations should be ahead of the game in terms of provision, notwithstanding insurance and provision of sufficient nuclear material.
PRRT is only available at a few cancer centres in Canada. It can only be used with special approval from Health Canada or by taking part in a clinical trial
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. On 21 Nov 2017, Unicorn Foundation New Zealand announced that Pharmac, the New Zealand government agency that decides which pharmaceuticals, have recommended that PRRT 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. This recommendation will be discussed at the PTAC meeting Feb 2018 and I’ll update when known.
- 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
Middle East, Asia and the Far East
Turkey – Istanbul, Dr.Levent Kabasakal.
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.
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)”