About   |   Articles archive   |   Contact us!   |      |     

How Australia wins prostate cancer

Australia, Cancer, Medicine

Michael Hoffman, a professor and nuclear medicine expert at Peter McCallum Oncocenter, spoke about how close Australia is to replication of theranostication of prostate cancer.
So far, European and Russian operators of the nuclear medicine segment are only getting closer to theranoscience — a combination of radionuclide diagnostics and targeted therapy for cancer diseases — in other countries the technique has already attracted serious intellectual and financial resources. In the world, the prostate cancer (prostate cancer) is considered to be the hot spot of theranosity, and they are trying to identify and treat it with radiopharmaceuticals based on a protein - a prostate-specific membrane antigen (PSMA). The successes of researchers who have achieved an increase in life expectancy for patients with prostate cancer to three years have already attracted money from Big Pharma players - at the end of last year, Swiss Novartis spent $ 2.1 billion on the purchase of a specialized American startup. Peter McCallum Oncology Center and ten more clinics across the country. Vademecum noted thematic activities in Russia and abroad, and on the way interrogated one of the participants in the tests with passion.

Malignant neoplasms (prostate cancer) of the prostate gland, clinicians say, have become the object of theranostic for two reasons. First, this nosology ranks third in the world in terms of prevalence — the International Agency for Research on Cancer (IARC) estimated the prostate cancer in 1.3 million cases, that is, 7.1 million, in 2018. % of the total number of cancer patients detected. And in the structure of male mortality from ZN, this localization was in second place after lung cancer.

Secondly, the diagnosis and treatment of prostate cancer can be targeted by attaching radioactive isotopes to PSMA. This protein is contained in the cells of the prostate gland, and when the EIT is present, its concentration is noticeably (in proportion to the growth of the tumor) increases. PSMA even entered the United States and Europe as a marker several years ago into the basic screening kit, but because of overdiagnosis, doctors and experts refused such tests.

But PSMA was used in nuclear medicine. Simplified, the scheme looks like this: before the start of therapy, a scan is performed using PET / CT and a gallium-based drug, 68-Gallium-PSMA, and then the detected cancer cells are destroyed with the help of the Lutetium-based drug, 177-Lutetia-PSMA. The advantages of the technique are accuracy - radionuclide theranostic, in contrast to radiation and chemotherapy, allows you to avoid damage to healthy tissue - and performance in advanced cases of the disease. Monitoring of tumor dynamics is also carried out on PET with the help of radiopharmaceuticals 68 ‑ Gallium-PSMA.

“In international practice and at the stage of CI, there are other types of radiopharmaceuticals - for example, instead of Gaul, 18 ‑ Fluor or 177 ‑ Lutetium can be used for diagnostics only in small doses,” says Alexander Zverev, director of the Medradiopreparat plant. “But in theranostics, the combination of 68 ‑ Gallium + 177 ‑ Lutetia at this stage is, of course, the main subject of research in clinical trials.”

The most complete information about more than 39,000 medical organizations in Australia

In Russia, 68 ‑ Gallium, not to mention the combination with 177 ‑ Lutecium, has not yet received widespread use. Yes, and theranostics, as a technique, did not even enter into experimental practice. The preparation based on the isotope 68-Gallium is used in the Russian Scientific Center for Radiology and Surgical Technologies named. Academician A.M. Granova - more than 600 procedures are performed here annually.

In the autumn of 2018, PET-Technology announced the start of such scans in Yekaterinburg, and at the beginning of March 2019, 133 radionuclide studies were performed there. “The decision on the introduction of treatment with the help of 177 ‑ Lutetia PSMA on the basis of PET-Technology centers will be taken at the end of 2019,” the company told Vademecum.

An active pharmaceutical substance based on 177 ‑ Lutetia from Medradiopreparat is at the registration stage, says Alexander Zverev. The radiopharmaceutical itself can be synthesized on the territory of the medical institution if regulatory conditions are created for this. While no one goes further experiments - THREAD them. S.P. Kapitsa, for example, organized the Center for Personalized Nuclear Medicine at Ulyanovsk State University, where he began to produce 177-Lutetia-PSMA. From this year, it is planned to treat 100-120 patients per year.

The founder of AO Meditsina, Grigoriy Roytberg, is now going to substantively develop the methodology. Now the head of the author's clinic is busy building the Center for Nuclear Medicine and Theranostic in Khimki, Moscow Region. “What attracted me to teranostike? Take, for example, such a common disease as prostate cancer. Unfortunately, the main part of such patients goes to medical institutions at the third or fourth stages, and no one wants to lead them, ”said Academician Roitberg last fall in an interview with Vademecum.

Are eyeing the direction and the European Medical Center. According to the EMC Director-General Andrei Yanovsky, theranostic, of course, not immediately, but may appear in the oncology complex created on the basis of the 63rd GKB in Moscow.

However, without systemic financing and liberalization of regulations on the technical arrangement of nuclear medicine facilities, there is no need to talk about the massive introduction of theranostics. According to market participants, one RFP introduction can cost approximately 350 thousand rubles, and the entire course of treatment can cost about 2 million, which is comparable to the tariffs for high-tech medical care, not immersed in the basic program of OMS.

The need to apply the methodology in the country is very significant: in 2017, according to the data of the Moscow National Research and Design Institute. P.A. Herzen, recorded 150.2 thousand cases of prostate cancer per 100 thousand population. The 35,000 new patients registered annually in 19–23% of cases show III – IV stage of the disease.

It should be noted that in the world, theranostica is only ‑ only included in the practice, and then in the status of clinical studies. According to the ClinicalTrials.gov portal, 68-Gaul-PSMA CI for prostate cancer have been completed in the United States, the Netherlands, Sweden and Canada. In combination with the 177 ‑ Lutecium, only a few CIs are conducted - in Italy, Australia and the USA. In one of these tests, sponsored by the American biotechnology company Endocyte, in phase II, 50 patients showed a median survival rate of 7.6 months. Having passed under the control of Novartis, the company launched Phase III, a multicenter randomized study that will involve up to 750 patients.

Among the leaders in the development of directions should be called Peter McCallum Cancer Center - Australia's largest specialized public health facility. The first phase of CPI therapy of prostate cancer was launched here three years ago, now 130 patients are involved in the study across the country. The curators of CI reported in medical journals on the average survival rate up to 13 months. The project leader, a specialist in nuclear medicine, Professor Michael Hoffman told Vademecum about the clinical results and business prospects of his undertaking.

- How long have you been practicing teranostication in Australia?

- The first in the country began to develop this topic oncology Peter McCallum. Since 2005, a group of rare neuroendocrine tumors has been treated here with the help of the drug 177 ‑ Lutetium ‑ Dotatate. Now in Australia in all cities - in Melbourne, Sydney, Brisbane, Adelaide, Perth - there are branches and centers that use this radiopharmaceutical in the treatment of neuroendocrine oncological diseases. Over the past years, we have treated hundreds of these patients, but neuroendocrine tumors are extremely rare, so five years ago we set a new goal - theranostic in prostate cancer, a much more common type of tumor. Moreover, it is one of the main causes of death for men with cancer in Australia.

- How did you do radionuclide therapy?

- I have been involved in nuclear medicine at the Peter McCallum Center for 10 years. In addition to PET diagnostics, which I always liked, I was interested in the therapeutic aspect of working with radiopharmaceuticals. And in the oncology center, I first practiced theranostication of neuroendocrine tumors, and then turned to the possibilities of radionuclide therapy for malignant tumors of the prostate. Now this is the main goal of my research. What we are doing in this area is different from the practice of other medical centers, where they are engaged in theranostication of prostate cancer. For example, in Germany, this therapy is carried out only individually for a small number of patients and therefore cannot provide relevant data on the effectiveness of treatment. We want to prove the advantages of the method to fellow oncologists and make it widely available.

- What is the essence of the method?

- Infrastructure and technology are the same as for theranostic neuroendocrine tumors, 177 ‑ Lutetium is also used, but the effect is different. The radiopharmaceutical molecule is attached to a prostate-specific membrane antigen, the content of which in prostate cancer is significantly increased in the tumor tissues, respectively, the drug acts as a target. Diagnostics, and we have been dealing with it since 2014, is being carried out using a special radiopharmaceutical 68-Gallium-PSMA, and in 2015, we began to carry out therapy with the drug 177-Lutetia-PSMA. In both cases, the PSMA molecule is used, only labeled with different radioactive substances.

The most comprehensive catalog of hospitals, pharmacies, dentists and other doctors in Canada.

The scheme is as follows: 68 ‑ Gallium is injected intravenously, “highlighting” PSMA, that is, demonstrating the localization of cancer cells on a PET ‑ scanner. Such an examination, by the way, can be performed at any stage of prostate cancer. We also inject the drug 177 ‑ Lutetium intravenously, and it also detects cancer cells from PSMA and destroys them. The radiation dose is very high - the average range for beta particles is about 1 mm. But the method allows to deliver the drug exactly to the target, wherever the cancer cells are located.

- From what sources and to what extent were the clinical studies of the method funded?

- Search and obtain resources for CI have demanded from us considerable efforts. I’m talking about resources, because as a result we don’t need financing as such. We were able to negotiate with the Australian Nuclear Science and Technology free shipment of 177 ‑ Lutetia from Sydney. The partners understand the prospects of the potential market, therefore they agreed to provide us with Lutetii for CI, and this is the most expensive part of the treatment. PSMA is produced in Germany, the manufacturer was also glad to participate in CI. We carry out the synthesis of the drug here, on the basis of our center, so no additional funding was required for this. The center receives state support, the hospital also earns money, all this completely covers the main items of expenditure - staff salaries and costs for administration and patient care. This is a unique situation, since the organization from scratch of conditions for such CIs would be extremely costly.

Patients, by the way, also do not pay anything for participation in CI, the only restriction is that patients of Peter McCallum Oncology Center with progressive metastatic castration-resistant prostate cancer should be involved. Simply put, with prostate cancer in stage IV, when all traditional methods of treatment no longer help. We are at the beginning of the road, as the standard practitioners have already recommended themselves for a long time, and it is very difficult to push through the new treatment method if you have not proved its effectiveness. Now that we have data on how this works on patients at this stage, our goal is to provide treatment at ever earlier stages in the development of the disease, but this is a long process.

- How many patients are currently involved in CI?

- We started in the format of a prospective CI - first we recruited 30 study participants, then we expanded the audience to 50 patients. It was about men who were not helped by chemotherapy with drugs such as docetaxel, enzalutamide and abiraterone. That is, the standard techniques did not work with these patients, and they simply had no options other than palliative care. We included them in the study and got very good results, comparable with the data of our colleagues from Germany.

We are now launching a larger, randomized trial that will involve 200 patients in 11 centers throughout Australia. We assign Lutetium to one group of patients selected at random, the second - second-line chemotherapy. 130 people from the planned 200 have already been involved in CI. This study has been lasting for 12 months and is showing decent results. We plan to complete the CI this year, and next year we will have to submit a report.

- In 2018, you reported that more than half of the patients participating in CI had a PSMA level of at least 50%. What does this mean in terms of survival?

- Of the 50 patients who received treatment, the rate of PSMA fell in 64% - we consider this a favorable result. In some patients, PSMA decreased to an insignificant level, but over time there was a relapse. The average survival rate of CI participants was 13 months, but many of those who responded to therapy lived much longer. There are patients who were treated in 2015 and are still alive, but without proper control outside the study it is difficult to give exact figures on survival. In addition, we do not yet have comparative data with the results of second-line chemotherapy to say exactly how our radionuclide method is the best alternative to it.

- How does treatment with Lutetium affect the patient's quality of life?

- The therapy is very well tolerated, it is targeted, that is, a minimum of the radiopharmaceutical gets into healthy tissues. Most patients do not feel side effects, on the contrary, they quickly begin to feel better - pain syndrome decreases, more energy appears.

A side effect can be dry mouth, but because of this we have never stopped treatment. Sometimes we observe a drop in the level of blood cells, but this, you see, is incomparable with the side effects of chemotherapy. This can be said right now, soon we will be able to confirm this with the specific data of a randomized comparative CI. In addition, our patients do not need hospitalization.

- Can you conduct such a radionuclide therapy on an outpatient basis?

- Australia is strong in the field of nuclear medicine, including due to the fact that we have a very favorable legal framework that allows the use of radioactive molecules on an outpatient basis. The center has a special infrastructure - cabins with lead screens for patients, allowing staff not to come into contact with large doses of radiation, and so on.

After the injection, the patient is “radioactive” for four hours and therefore has to be in a special room. Then the radiation "goes" into the tumor, the remains are excreted in the urine, we measure the level of radiation and in most cases we let the patient go home. I know that in Europe, in the same Germany, patients must stay in the hospital for several days, which significantly increases the cost of treatment. I do not know how things are in Russia.

- Our regulations are also very tough.

- I heard that in the USA it is also not easy to develop this area. Drugs must be registered - this is supervised by the FDA. We can create drugs right in the hospital and use them in a comfortable patient environment, so we were able to quickly start the study.

- How many patients, according to your calculations, need such treatment?

- Prostate cancer is among the TOP4 causes of death among men in the world. In the early stages, cancer is less aggressive, a person may die with it, but not from it. However, it often happens that the disease enters an aggressive stage and leads to death. I think in Australia we are talking about tens of thousands of men who need this kind of treatment. From a business point of view, this is a huge market.

- Someone from Big Pharma is already interested in this topic?

- As far as I know, the rights to the 177 ‑ Lutetium ‑ PSMA ‑ 617 molecule were recently acquired by the Swiss Novartis [through the uptake of the American Endocyte. - Vademecum]. Since now the game is such a large pharmaceutical company, it is worth assuming that, as soon as the CI is completed, the drug will enter the market. According to my most approximate estimates, a single dose of the drug will cost $ 50,000. This, of course, is not cheap, but cheaper than the courses of treatment of chemotherapy or, for example, proton therapy.

- Isn't it easier then to manufacture the drug right in the hospital, as you do?

Find all partners in Canada will help you directory allcanada.org

- Nuclear reactors, which, as ANSTO, generate 177 ‑ Lutetium, are few in the world - only about five. It is good that we have a local source of Lutetia and the competences for the production of the drug in the hospital. The final product does not come to us in a beautiful box. But not for all such a path is possible. In the future, the drug will be manufactured in batches and shipped around the world. Lutetia has a half-life of seven days, so the drug can be delivered safely. I think in five years it will be possible to buy it anywhere.

- When your treatment is confirmed and approved, will compulsory health insurance cover it in Australia?

- In fact, the treatment is not so expensive. We are talking about the exact number of cycles: diagnosis + therapy. In total, this is 4-6 doses of Lutetia, which is cheaper than chemotherapy. While I do not have exact figures, but I do not expect that our treatment method will be more expensive than the existing ones, rather, it will turn out to be cheaper. I know that in some countries, for example, in India and South Africa, such treatment is already available on a paid basis, and it is cheaper than chemotherapy. Therefore, patients even at earlier stages tend to complete the course in order to save money. In other countries, the situation, of course, may be quite different.

- How in the scientific world relate to the practice of India and South Africa? They are already selling the service, while others are just testing.

“I think that in order to make treatment accessible, we need approval from our fellow oncologists and other specialists. Without evidence that convincingly demonstrates that therapy works and is better than existing practices, they will not recommend such treatment to patients. What our oncologists need now is evidence from randomized clinical trials. Without the results of such tests to replicate the method of treatment will not work, it will remain niche. Patients will search for information on the Internet, then fly to some center in India. But it should be available to everyone, not just in one or two centers. And theranostics of prostate cancer has every chance.

Find the best lawyers in the United States and Canada, please visit: attus.org and attcan.org